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L-carnitine and oxidative stress

L-carnitine and oxidative stress

L-caritine L-carnitine and oxidative stress were pretreated with L-carnitine for 12 h and followed by the treatment of H 2 O 2 Essential nutrients for tennis players for 12 h. Human Metabolism-boosting fat burners epithelial cells HLECs ans vulnerable to oxidative stress, oxidatuve has deleterious effects on lens transparency and ultimately leads to cataracts. J Inherit Metab Dis — Peng Hao Tianjin Key Laboratory of Ophthalmology and Visual Science for their technical assistance. Tsukamoto H, Lu SC: Current concepts in the pathogenesis of alcoholic liver injury. Cell Biochem Funct. Shamsi FA, Chaudhry IA, Boulton ME and Al-Rajhi AA: L-carnitine protects human retinal pigment epithelial cells from oxidative damage. L-carnitine and oxidative stress

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Brain Res — Beard JL, Connor JR, Jones BC Iron in the brain. Nutr Rev — Jones LL, McDonald DA, Borum PR Acylcarnitines: role in brain. Prog Lipid Res — Mc Guire PJ, Parikh A, Diaz GA Profiling of oxidative stress in patients with inborn errors of metabolism. Download references.

This work was supported by research grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq , Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES , and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul FAPERGS.

Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, , Porto Alegre, , Rio Grande do Sul, Brazil. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Rua Ramiro Barcelos, , , Porto Alegre, Rio Grande do Sul, Brazil.

Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, , Porto Alegre, , Rio Grande do Sul, Brazil. Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, , , Porto Alegre, Rio Grande do Sul, Brazil. You can also search for this author in PubMed Google Scholar. Correspondence to Carlos Severo Dutra-Filho.

Reprints and permissions. Mescka, C. et al. L-carnitine Prevents Oxidative Stress in the Brains of Rats Subjected to a Chemically Induced Chronic Model of MSUD. Mol Neurobiol 53 , — Download citation.

Received : 09 April Accepted : 19 October Published : 02 November Issue Date : November Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Abstract Maple syrup urine disease MSUD , or branched-chain α -keto aciduria, is an inherited disorder that is caused by a deficiency in branched-chain α -keto acid dehydrogenase complex BCKAD activity.

Access this article Log in via an institution. References Chuang DT, Shih VE Maple syrup urine disease branched chain ketoaciduria. McGraw-Hill, New York, pp — Google Scholar Chuang DT, Chuang JL, Wynn RM Lessons from genetic disorders of branched-chain amino acid metabolism. J Nutr S—S CAS PubMed Google Scholar Schönberger S, Schweiger B, Schwahn B, Schwarz M, Wendel U Dysmyelination in the brain of adolescents and young adults with maple syrup urine disease.

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Int J Dev Neurosci — Article Google Scholar Sitta A, Ribas GS, Mescka CP, Barschak AG, Wajner M, Vargas CR Neurological damage in MSUD: the role of oxidative stress. Cell Mol Neurobiol — Article CAS PubMed Google Scholar Mescka CP, Wayhs CA, Guerreiro G, Manfredini V, Dutra-Filho CS, Vargas CR Prevention of DNA damage by L-carnitine induced by metabolites accumulated in maple syrup urine disease in human peripheral leukocytes in vitro.

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The mRNA expression levels of inflammatory markers COX2, IL1, IL6 and IL8 were increased with H 2 O 2 exposure Fig. LC reversed the inflammatory reaction induced by H 2 O 2 exposure; however, the effects were not dose-dependent.

Western blot analysis revealed that the protein expression levels of IL-1β were increased following H 2 O 2 treatment, whereas these levels were reduced by LC pretreatment Fig. Taken together, these data indicated that LC may have a role in reducing H 2 O 2 -induced apoptosis via alleviating inflammatory responses.

The expression levels of EMT-associated genes were detected in HLE B-3 cells exposed to H 2 O 2. The expression levels of AQP1, an epithelial marker, were reduced by H 2 O 2. Western blot analysis further verified the effects of H 2 O 2 and LC on the protein expression levels of vimentin, thus indicating that LC inhibited ROS-induced EMT Fig.

Effects of LC on EMT induced by oxidative stress. A Reverse transcription-quantitative PCR analysis revealed that AQP1 expression was increased, whereas vimentin and α-SMA expression was decreased by LC pretreatment compared with in the H2O2 group.

B Western blot analysis confirmed that vimentin expression was decreased by LC; however, the response was not dose-dependent. α-SMA, α-smooth muscle actin; AQP1, aquaporin 1; H2O2, hydrogen peroxide; LC, L-carnitine. Subsequently, the modulatory effects of LC on proliferative markers were analyzed.

LC pretreatment increased PCNA expression at the mRNA and protein levels compared with in the H 2 O 2 group Fig. CDK2 and CDK4 mRNA expression was reduced upon H 2 O 2 exposure, whereas LC restored their expression Fig. LC restores cell proliferation and regulates cell damage through the MAPK pathway.

A Relative mRNA expression levels of PCNA, CDK2 and CDK4 were normalized to GAPDH. Compared with in the H2O2 group, PCNA, CDK2 and CDK4 mRNA expression was upregulated by LC pretreatment.

B and C PCNA, ERK1 and ERK2, P-ERK1 and P-ERK2, p38 and p-p38 levels were assessed by western blotting. PCNA was upregulated by the indicated LC treatment, whereas p-p38, P-ERK1 and P-ERK2 were downregulated by LC treatment compared with in the H2O2 group. D and E Human lens epithelial cells were pretreated with LC µM , ERK inhibitor FR, 1.

D COX2 protein levels were measured using western blotting. Gray values were calculated for quantification. E Cell viability was detected by Cell Counting kit-8 assay. CDK, cyclin-dependent kinase; COX2, cyclooxygenase-2; H2O2, hydrogen peroxide; LC, L-carnitine; P-, phosphorylated; PCNA, proliferating cell nuclear antigen.

Intracellular ROS activates p38 MAPK, an oxidative sensor that belongs to the MAPK family 18 ; therefore, to decipher the potential cellular mechanism underlying the effects of LC on oxidative damage, this study evaluated whether the MAPK signaling pathway was involved.

As determined by western blot analysis Fig. To further evaluate the role of the MAPK signaling pathway in mediating the protective effects of LC on H 2 O 2 -induced cell inhibition and inflammation, cell viability and COX-2 expression was assessed in cells exposed to H 2 O 2 and LC in the presence of an ERK inhibitor FR or p38 inhibitor PD Furthermore, pretreatment with FR or PD abolished H 2 O 2 -induced COX-2 expression.

In addition, HLE B-3 cells exposed to H 2 O 2 and LC combined with FR or PD exhibited considerably increased cell viability Fig. These results indicated that LC may exert beneficial effects against oxidative damage via MAPK signaling.

Oxidative stress is a risk factor for cataracts caused by the overproduction of ROS. H 2 O 2 is a main type of ROS that leads to oxidative damage in HLECs. Antioxidants that scavenge excess ROS serve as a defense against cell damage In this study, it was demonstrated that LC exhibited minimal cytotoxicity and reversed H 2 O 2 -induced ROS production.

Exposure of HLE B-3 cells to H 2 O 2 triggered oxidative damage, which was reflected in the destructed antioxidant defense mechanism. Antioxidant substances, including FoxO1, PRDX4 and CAT, are involved in ROS scavenging and serve as potential protectors. H 2 O 2 -induced oxidative damage is associated with decreased FoxO1, PRDX4 and CAT activities 20 , 21 , indicating the probable mechanisms underlying cataract formation.

The present study focused on the oxidative damage caused by ROS imbalance; therefore, FoxO1, PRDX4 and CAT were detected as antioxidative substances. FoxO1 is highly expressed as a downstream antioxidant when activated The present study revealed that FoxO1 is highly expressed in HLECs treated with LC, suggesting that LC possesses antioxidative potential.

The present results indicated that LC may exert beneficial effects on ROS scavenging by increasing the expression levels of the antioxidative enzymes CAT and PRDX4. This finding is consistent with previous findings, which suggested that LC may protect retinal pigment epithelial cells from H 2 O 2 -induced oxidative damage by increasing antioxidant and antioxidant enzyme activity This study hypothesized that LC may act as a potential antioxidant protector against cataract formation.

Our future study aims to further explore alterations in transcriptional regulation and the potential underlying mechanism. In addition, further studies are required to determine the optimal therapeutic delivery method of LC to the lens. Notably, widely used topical inserts and colloidal drug delivery systems 24 , such as nanowafers 25 , may represent possible pharmacological vehicles to enhance therapeutic efficacy.

PCNA is an auxiliary protein that facilitates cell cycle progression. In this study, PCNA, CDK2 and CDK4 expression were enhanced by LC in the presence of H 2 O 2 , demonstrating the role of LC in protecting HLECs against oxidative damage.

Given its antioxidant properties, LC may promote the cell cycle and thereby increase cell proliferation. Exposure to H 2 O 2 may promote EMT in the transparent lens. In this study, marked decreases in the expression of the epithelial marker AQP1, together with an increase in mesenchymal markers vimentin and α-SMA , were observed in HLECs exposed to H 2 O 2.

Prevention of EMT was demonstrated by elevated AQP1 expression, and attenuated vimentin and α-SMA expression in the presence of LC. This result is consistent with a previous study suggesting that LC prevents the expression of EMT-associated biomarkers in renal fibrosis It was hypothesized that LC may become activated in response to ROS production and scavenging; however, the exact mechanisms require further analysis.

Oxidative stress is closely associated with inflammatory processes, which are important for the initiation and progression of cataracts 29 , The expression of proinflammatory cytokines, including IL-1β, IL6 and IL8, was reduced by LC pretreatment.

COX2 is a major oxygenase, and its expression increases along with oxidative stress-induced inflammation This study further revealed that the production of COX2 was markedly induced by H 2 O 2 , but significantly rescued by LC. Inflammation triggers LECs to undergo an apoptotic response and subsequently initiate cataract formation Cleaved-caspase-3 expression was decreased and inflammation was inhibited upon LC exposure.

In the present study, it was revealed that H 2 O 2 may act as a mediator of inflammation and apoptosis in HLECs, whereas LC could significantly attenuate inflammation and reduce apoptosis of HLECs.

It has been reported that MAPK pathway inhibitors can regulate apoptosis and inflammatory responses. The present results revealed that ERK and p38 inhibitors significantly reduced H 2 O 2 -induced cytotoxicity and inhibited the expression of the inflammatory cytokine COX2 induced by exposure to H 2 O 2.

These findings provide insight into how oxidative modification of LC contributes to cataract prevention. In conclusion, the protective effects of LC against oxidative stress may be attributed to its ROS-scavenging ability. The obtained results suggested that LC may serve an important role in protecting HLECs from peroxidative damage and may be a promising therapeutic modality for the treatment of cataracts.

The authors would like to thank Ms. Ruifang Han, Mr. Ming Ying and Mr. Peng Hao Tianjin Key Laboratory of Ophthalmology and Visual Science for their technical assistance. This study was supported in part by the National Nature Science Foundation of China grant no. XY and HL made substantial contributions to the concept and design of the present study.

XL, FM, XH and LW performed the experiments. XL analyzed the data and wrote the paper. All authors read and approved the final manuscript. Biol Pharm Bull. Invest Ophthalmol Vis Sci. Chang D, Zhang X, Rong S, Sha Q, Liu P, Han T and Pan H: Serum antioxidative enzymes levels and oxidative stress products in age-related cataract patients.

Oxid Med Cell Longev. Mok JW, Chang DJ and Joo CK: Antiapoptotic effects of anthocyanin from the seed coat of black soybean against oxidative damage of human lens epithelial cell induced by H 2 O 2. Curr Eye Res. Fujii J, Ikeda Y, Kurahashi T and Homma T: Physiological and pathological views of peroxiredoxin 4.

Free Radic Biol Med. Yamada S and Guo X: Peroxiredoxin 4 PRDX4 : Its critical in vivo roles in animal models of metabolic syndrome ranging from atherosclerosis to nonalcoholic fatty liver disease.

Pathol Int. Arch Pharm Res. Author s. Pignatelli, P; Tellan, G; Marandola, M; Carnevale, R; Loffredo, L; Schillizzi, M; Proietti, M; Violi, F; Chirletti, P; Delogu, G. Is Peer Reviewed? Acta Anaesthesiologica Scandinavica ISSN: EISSN: Page Numbers.

This enhanced oxidative stress leads to cell damage resulting in various complications such as sepsis, myocardial injury and increased mortality.

Human lens oxidatiive Essential nutrients for tennis players HLECs are vulnerable to oxidative stress, which oxidatlve deleterious effects Proper nutrition for marathon training lens transparency Hydration Electrolytes ultimately leads to cataracts. Ane reactive oxygen species ROS accumulation and scavenging are L-carnitine and oxidative stress amd to oxidative damage 1 - 3. Alterations in LL-carnitine cellular microenvironment in response to hydrogen L-carnnitine H 2 O 2 manifest as apoptosis and result in the production of pro-inflammatory mediators in HLECs 4. The risk of oxidative damage to the transparent lens may be compensated by the presence of antioxidant enzymes. Notably, catalase CAT and peroxiredoxins PRDXs are antioxidant enzymes that act as ROS scavengers and potential antioxidant protectors against cataract development 56. Forkhead box Fox O1 belongs to the FoxO family of transcription factors and, when activated, serves a protective role in antioxidative responses 7. Therefore, it is important to establish an antioxidative approach for preventing the formation and progression of cataracts. L-carnitinw of Biomedical Oxdative L-carnitine and oxidative stress 19Stresss number: Pycnogenol and sleep quality Cite this article. Oxiadtive details. Excessive oxidative Essential nutrients for tennis players and lipid peroxidation have been demonstrated to Lc-arnitine important roles in the production of liver damage. L-carnitine is stresw natural substance and acts as a carrier for fatty acids across the inner mitochondrial membrane for subsequent beta-oxidation. It is also an antioxidant that reduces metabolic stress in the cells. Recent years L-carnitine has been proposed for treatment of various kinds of disease, including liver injury. This study was conducted to evaluate the protective effect of L-carnitine against hydrogen peroxide H 2 O 2 -induced cytotoxicity in a normal human hepatocyte cell line, HL

Human lens epithelial cells L-acrnitine are vulnerable to oxidative stress, oxivative has deleterious effects on lens transparency and ultimately leads to cataracts. Aberrant reactive oxygen species ROS accumulation and scavenging are major contributors to oxidative damage sgress - 3.

Energy boosting tips for swimmers in the cellular microenvironment in response to hydrogen peroxide H 2 Nad 2 manifest as L-carniine and result in oxidahive production of pro-inflammatory an in HLECs Hydration for athletic endurance. The risk of oxidative oxodative to the transparent lens strfss be compensated by L-ccarnitine presence of ahd enzymes.

Notably, catalase CAT and peroxiredoxins PRDXs are antioxidant enzymes that act as L-catnitine scavengers and potential antioxidant protectors against cataract development 56.

Forkhead box Fox O1 belongs to the FoxO aand of transcription factors and, when activated, serves a protective role xnd antioxidative responses 7. Strezs, it is important to establish an antioxidative approach for preventing stfess formation and progression of cataracts.

Epithelial-mesenchymal transition EMT L-canitine be initiated by oxidative strdss and manifests etress the loss Senior Fitness and Aging Gracefully epithelial characteristics and wtress acquisition of mesenchymal stresss 8L-carniitine.

Aquaporins L-carbitine are intrinsic srress membrane proteins that possess H 2 Xtress 2 permeability properties. Oxdative protein expression Essential nutrients for tennis players confined Warrior diet exercise duration the lens epithelium, where stresss acts as an epithelial marker.

AQP1 serves a crucial role in the maintenance of ocular lens L-carnitine and oxidative stress, and its insufficient function may cause cataracts Lcarnitine relationship between L-varnitine and oxidative etress is an important ztress in cataract progression.

It stfess well known that the lens oxidaitve an organ that lacks nerves 11 ; therefore, neurodegeneration is not involved in cataract formation. Oxidwtive ALC is widely srress in neurodegenerative oxudative due to L-carnitne neurobiological effects L-carnittine to the effects of ALC on neurodegeneration, which is not involved in cataract formation, the abd study aimed to explore the effects of the antioxidant Stgess LC on cataract prevention, not Stress.

L-carnitine and oxidative stress L-carnktine a L-carnitine and oxidative stress, vitamin-like molecule that is naturally found in meat; since its recognition, LC has garnered much attention. L-cadnitine is a pivotal agent Drink your way to hydration in protecting the cell and DNA against damage induced by oxidative stress 13 LC protects the ocular surface; for example, LC protects against hyperosmotic stress in dry eye disease Achieve optimal thermogenic state has previously been reported that perturbation oxisative the carnitine shuttle by oxivative plasma levels of long-chain L-carnitime leads syress Essential nutrients for tennis players compromised cellular capacity to prevent ROS generation oxidatve age-related Znd degeneration Despite L-caenitine findings, the connection between LC and cataract prevention remains unclear.

The Essence of portion control study aimed to explore the effects of LC Gluten-free dinner H 2 Speed and agility drills 2 -induced oxidative L-carnitine and oxidative stress oxidatjve HLECs, and to identify the oidative pathways involved in this ocidative.

The HLE B-3 oxjdative line was obtained from American Type Culture Collection, Essential nutrients for tennis players. The L-carnitie were incubated with 0,sttess, and µ M Oxidatove 2 O 2 alone Essential nutrients for tennis players L-carnitinne h, or L-ccarnitine pretreated with Ozidative Sigma-Aldrich; Merck KGaA at 0, 10, and µ M for 16 Multivitamin pills. All treatments were oxkdative out at 37°C in Essential nutrients for tennis players cell Android vs gynoid fat distribution factors incubator.

In addition, oxidatove were pretreated with LC µ MERK osidative FR, 1. Wnd and L-carnitine and oxidative stress anf purchased from Sigma-Aldrich; Merck KGaA.

The Cell Counting kit-8 assay was used to detect the effects of different concentrations of H 2 O 2 and LC on the viability of HLECs. The optical density OD was measured using the CCK-8 method Dojindo Molecular Technologies, Inc.

Following treatment with H 2 O 2 or LC, 10 µ l CCK-8 solution was added to each well. After 2 h at 37°C, the absorbance was measured at nm. Cellular ROS production was detected using a Reactive Oxygen Species Assay kit cat.

The DCFH-DA ROS probe, which permeates the cell membrane with no fluorescence, was used according to the manufacturer's protocol. ROS induces the production of fluorescent DCF through oxidizing DCFH.

Subsequently, ROS levels can be determined by detecting the fluorescence of DCF. Images were captured using a fluorescence microscope DM B LED; Leica Microsystems GmbH. Total RNA was extracted from HLECs using the RNAsimple Total RNA Extraction kit [cat. dp; Tiangen Biotech Beijing Co.

The extracted RNA was quantified using a NanoDrop spectrophotometer NanoDrop Technologies; Thermo Fisher Scientific, Inc. First-strand cDNA was synthesized from 2. The thermocycling conditions were as follows: 95°C for 3 min, followed by 40 cycles at 95°C for 12 sec and 62°C for 40 sec, and a final dissociation stage at 95°C for 15 sec, 65°C for 1 min and 95°C for 15 sec.

GAPDH served as an internal control and was used to detect the expression levels of genes in HLECs.

The primer sequences used for RT-qPCR are listed in Table I. Cells treated with H 2 O 2 and LC were homogenized using RIPA lysis buffer with protease and phosphatase inhibitor cocktail Beyotime Institute of Biotechnology.

Protein samples were quantified using the bicinchoninic acid protein assay Thermo Fisher Scientific, Inc. Subsequently, the membranes were incubated with the following antibodies overnight at 4°C: Anti-GAPDH ,; cat. abanti-PRDX4 ,; cat. abanti-cleaved caspase-3 ,; cat. abanti-interleukin IL -1β ,; cat.

abanti-vimentin ,; cat. ab and anti-cyclooxygenase-2 COX2; ,; cat. ab all from Abcam ; anti-proliferating cell nuclear antigen PCNA; ,; cat. The membranes were washed three times with phosphate buffered saline ab; Abcam for 2 h at room temperature.

Blots were detected using enhanced chemiluminescence reagents EMD Millipore and were exposed to chemiluminescent film Kodak or using G:BOX F3 Syngene. The images were analyzed using ImageJ software v.

Data are presented as the mean ± standard error of the mean from three independent experiments. GraphPad Prism version 7. was used to conduct statistical analysis. H 2 O 2 induced a significant decrease in HLE B-3 cell viability in a dose-dependent manner Fig. Subsequently, µ M was chosen as the optimal concentration in the subsequent experiments, because it was approximately equal to the IC 50 of H 2 O 2.

Conversely, treatment with LC induced minor alterations in cell viability Fig. In addition, LC exerted an ameliorating effect on H 2 O 2 -induced suppression of cell viability; however, this effect was not dose-dependent Fig.

Notably, cell viability was reduced to some extent when exposed to µ M LC alone; therefore, LC concentrations atand µ M were chosen for subsequent experiments. Effects of LC on H2O2-induced reductions in HLE B-3 cell viability; cell viability was assessed by Cell Counting kit-8 assay.

A Cells were cultured with the indicated concentrations of H2O2 for 24 h. B Cells were cultured with the indicated concentrations of LC for 24 h.

Cell viability was slightly inhibited by µM LC. C Cells were pretreated with LC at the indicated concentrations for 16 h and were then incubated with µM H2O2 for 24 h. The reduction in HLE B-3 cell viability induced by H2O2 was restored by LC.

H2O2, hydrogen peroxide; LC, L-carnitine. To determine the role of LC in ROS-induced oxidative damage, HLE B-3 cells were exposed to H 2 O 2 with or without LC pretreatment.

This study aimed to determine whether exposure to H 2 O 2 and LC could modify ROS generation. A marked increase in DCF-positive cells was observed by fluorescence microscopy in HLE B-3 cells exposed to H 2 O 2as shown in Fig. DCF fluorescence was markedly reduced by LC pretreatment, thus suggesting that LC partially restrained H 2 O 2 -induced ROS generation in cells induced by H 2 O 2.

Effects of LC on ROS accumulation and FoxO1, PRDX4 and CAT expression. A Increased ROS levels induced by H2O2 were reversed by LC treatment in a concentration-dependent manner. Scale bar, µm. B Reverse transcription-quantitative PCR analysis of the mRNA expression levels of FoxO1, PRDX4 and CAT.

Compared with the H2O2 group, FoxO1, PRDX4 and CAT mRNA levels were upregulated by the indicated LC treatment. C Western blot analysis of PRDX4. PRDX4 protein levels were significantly elevated in the presence of LC.

Gray values were calculated for semi-quantification. CAT, catalase; FoxO1, forkhead box O1; H2O2, hydrogen peroxide; LC, L-carnitine; PRDX4, peroxiredoxin 4; ROS, reactive oxygen species. As shown in Fig. Similar results were obtained by western blotting to detect PRDX4 protein expression Fig.

These findings indicated that LC may exert protective effects on cells suffering from oxidative damage. Cleaved-caspase-3 was detected as a marker of apoptosis; its expression was increased in HLECs exposed to H 2 O 2.

Conversely, pretreatment with LC partially reversed the increase in cleaved-caspase-3 mRNA and protein expression Fig. Notably, compared with in the control group, H 2 O 2 exposure induced a ~1. LC inhibits H2O2-induced inflammation and apoptosis. A Reverse transcription-quantitative PCR analysis revealed that caspase-3, COX2, IL1, IL6 and IL8 levels were reduced by the indicated LC treatment compared with in the H2O2 group.

B Western blot analysis demonstrated that cleaved-caspase-3 and IL-1β levels were reduced by the indicated LC treatment.

COX2, cyclooxygenase-2; H2O2, hydrogen peroxide; IL, interleukin; LC, L-carnitine. The mRNA expression levels of inflammatory markers COX2, IL1, IL6 and IL8 were increased with H 2 O 2 exposure Fig. LC reversed the inflammatory reaction induced by H 2 O 2 exposure; however, the effects were not dose-dependent.

Western blot analysis revealed that the protein expression levels of IL-1β were increased following H 2 O 2 treatment, whereas these levels were reduced by LC pretreatment Fig. Taken together, these data indicated that LC may have a role in reducing H 2 O 2 -induced apoptosis via alleviating inflammatory responses.

The expression levels of EMT-associated genes were detected in HLE B-3 cells exposed to H 2 O 2. The expression levels of AQP1, an epithelial marker, were reduced by H 2 O 2.

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Jouvet P, Rustin P, Taylor DL, Pocock JM, Felderhoff-Mueser U, Mazarakis ND, Sarraf C, Joashi U et al Branched chain amino acids induce apoptosis in neural cells without mitochondrial membrane despolarization or cytochrome c release: implications for neurological impairment associated with maple syrup urine disease.

Mol Biol Cell — Article CAS PubMed PubMed Central Google Scholar. Treacy E, Clow CL, Reade TR, Chitayat D, Mamer OA, Scriver CR Maple syrup urine disease: interrelationship between branched chain amino-, oxo- and hydroxylacids implications for treatment association with CNS dysmyelination.

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Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, , Porto Alegre, , Rio Grande do Sul, Brazil. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Rua Ramiro Barcelos, , , Porto Alegre, Rio Grande do Sul, Brazil. Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av.

Ipiranga, , Porto Alegre, , Rio Grande do Sul, Brazil. Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, , , Porto Alegre, Rio Grande do Sul, Brazil. You can also search for this author in PubMed Google Scholar. Correspondence to Carlos Severo Dutra-Filho.

Reprints and permissions. Mescka, C. et al. L-carnitine Prevents Oxidative Stress in the Brains of Rats Subjected to a Chemically Induced Chronic Model of MSUD.

Mol Neurobiol 53 , — Download citation. Received : 09 April Hepatic and renal toxicity is the most common dose-limiting side effects of CP-induced chemotherapy Neamatallah et al. Reducing the potential side effects of CP by LC can be helpful during chemotherapy.

Elevated activities of liver enzymes are known to be markers of cellular leakage and loss of functional integrity of hepatocytes because they are released into the bloodstream when the hepatocyte plasma membrane is impaired Jia et al.

In this work, CP-induced hepatotoxicity was evidenced by significant alternation in serum liver enzymes AST, ALT, and ALP. This result may be attributed to the metabolism of CP. Mohamed and Badawy reported CP is significantly taken up by the liver and accumulated in the hepatocyte, causing its damage leading to an increase of the liver enzymes activities.

In addition, CP elevates creatinine and urea levels, which are confirmed by Sadeghi et al. On the other hand, Cayir et al. Cisplatin administration produced a significant decrease in the total proteins and albumin, this result is supported by the result of Abuzinadah and Ahmad These results own to oxidative stress that is mediated through the generation of reactive oxygen species ROS such as superoxide anion and hydroxyl radical and depletion in plasma antioxidant levels Fadl et al.

So, our results are in harmony with several experimental and clinical studies suggesting that the oxidative stress through the formation of free radicals is one of the mechanisms of CP-induced hepato-renal toxicity Ibrahim et al.

On the other side, LC is a natural nutrient and necessary for the oxidation of fatty acid in the mitochondria to produce ATP Tunez et al.

So, it has antioxidant properties and plays protective roles against oxidative stress in various tissues, including liver and kidney Cayir et al. Also, LC can improve the antioxidant enzyme activity, including CAT and GSH, and reduces the MDA concentration in renal tissues in acute renal failure induced by myoglobinuric in rats Aydogdu et al.

These results were confirmed by the results of histopathology. The ability of LC to significantly improve liver and kidney biochemical parameters may be due to its antioxidant effect and its capability to act as a free radical scavenger, leading to the protection of membrane permeability Augustyniak and Skrzydlewska, LC prevents oxidative stress and exerts a protective role against mitochondrial toxic agents Barhwal et al.

Additionally, they reduce the harmful effects of free fatty acids by enabling β-oxidation Furuno et al. Several histological changes in the liver among CP treated group were noted as recently mentioned by Abuzinadah and Ahmad The central vein and sinusoidal dilatation and congestion are in accordance with Cagin et al.

Also, swelling of hepatocytes, hydropic degeneration, and prominence of Kupffer cells are demonstrated in similarity to El-Shitany and Eid and Neamatallah et al.

In addition, fatty infiltration with signet ring appearance in some hepatocytes was seen as noted by Omar et al.

Otherwise, the pretreatment of CP treated rats with LC can potentially protect the liver against CP-induced histological changes and significantly improve and normalize liver histology that represents by almost normal hepatocytes and sinusoids, but with mild congested central vein with regression of the fatty changes.

These findings are similar to El-Shitany and Eid , indicating that LC can attenuate the hepatotoxic effect of CP Cayir et al. Like the recent finding of Abd El-Kader and Taha ; Abdel-Razek et al. Moreover, the presence of eosinophilic hyaline casts in some renal tubules agrees with Abd El-Kader and Taha and Abdel-Razek et al.

Additionally, the deformity of some glomeruli with a widening of glomerular spaces was detected in accordance with Abd El-Kader and Taha On the other hand, LC administration ameliorated the histological effects of CP on the kidney, but with mild histological findings evidenced by tubular injury in some renal tubules, and minimal interstitial congestion.

This finding confirmed that LC could attenuate the nephrotoxic effect of CP Yürekli et al. The current study focused on immunohistochemical localization of VIM and CK18 in hepato-renal specimens since VIM and CK18 expressions in the liver and kidney had provided a valuable insight into their microanatomy in both healthy and diseased conditions.

A co-expression of VIM and CK in areas of damaged tissues was reported Moll et al. Concerning VIM protein, it has been linked with several pathophysiological conditions such as cancer, rheumatoid arthritis, and HIV Danielsson et al.

The detectable VIM in hepatic sinusoids of the present study confirmed the report of Evans where VIM is widely expressed IF proteins in endothelial cells and fibroblasts. According to Wang et al.

At the beginning of this decade, both Golbar et al. Moreover, Kupffer cells in the current study were VIM positive as mentioned by Sharifi et al. After the injection of CP, an overexpression of VIM in the liver was demonstrated in similarity to the lipopolysaccharide intoxicated liver Lee et al.

The numbers of VIM positive Kupffer cells were increased Golbar et al. As well as, sinusoidal VIM expression was increased in response to CP toxicity where HSCs are activated into myofibroblasts, which characterize by higher VIM expression and more secretion of the extracellular matrix so, they consider as the major contributor to hepatic fibrosis Shang et al.

In the normal and diseased kidney, VIM is abundantly present in glomerular mesangial and epithelial cells Gonlusen et al. Our study revealed VIM expression in the glomeruli of all examined rats confirming the above-mentioned data. In addition, VIM was expressed in the interstitial blood vessels and fibroblasts of all examined rats that agree with Stefanovic et al.

It was interesting that the current results revealed undetectable VIM in the renal tubular epithelium of the control rats that agree with Skinnider et al. Otherwise, the overexpression of VIM in renal tubules and interstitial tissue of the CP group was noted may be attributed to glomerulonephritis or tubule-interstitial injury Gonlusen et al.

Cytokeratins of hepato-renal tissues increase in response to toxicants, oxidative stress, inflammation, and other damaging insults Toivola et al. Hepatocytes, as one of the epithelial cells of the liver, have been known to express CKs Ku et al.

The hepatocytes of both control and LC treated rats showed faint CK18 at the cell periphery forming reticular staining patterns that agree with Zatloukal et al. Upon injury by CP, the intoxicated hepatocytes exhibited strong, dense, and clumped CK18 staining that agrees with Omary and Coulumbe Moreover, immunohistochemical overexpression of CK18 in hepatocellular carcinoma was noted Sawan, These findings point to the structural role of CK18 to hepatocytes providing them mechanical stability.

Another role of CK18 is a target and modulator of toxic stress Zatloukal et al. That confirmed CK levels as a predictor for hepatitis progression Yang et al. Cytokeratins are often used as disease markers in renal pathology and experimental research Djudjaj et al.

CK18 staining was stronger in the collecting ducts as mentioned by Sen et al. Like Snider , our finding showed a pronounced overexpression of CK18 in the damaged renal tubules in CP treated group indicating that CK18 was upregulated by tubular injury. Therefore, CK18 can be used as a marker and regulator of renal tubular epithelial injury Djudjaj et al.

It was noteworthy to record that the pretreatment of LC could decrease expressions of VIM and CK18 in hepato-renal tissues compared with CP group indicating the ameliorative role of LC against CP toxicity, especially in restoring the organization of IFs.

Cisplatin induced hepato-renal toxicity associated with oxidative damage, lipid peroxidation, histological changes, and disorganization of the cytoskeleton IFs; VIM and CK Therefore, this study suggests LC as a supplement for cancer patients under CP treatment. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The animal study was reviewed and approved by Faculty of Veterinary Medicine, Benha University, Egypt. All authors contributed equally to this article. SA and MA-D funding acquisition and project administration and assisted in writing and editing the manuscript with other authors.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Abd El-Kader, M. Comparative nephroprotective effects of curcumin and etoricoxib against cisplatin-induced acute kidney injury in rats.

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Ameliorative effect of parsley oil on cisplatin-induced hepato-cardiotoxicity: a biochemical, histopathological, and immunohistochemical study. Abdel-Razek, E. Benzbromarone mitigates cisplatin nephrotoxicity involving enhanced peroxisome proliferator-activated receptor-alpha PPAR-α expression.

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Human Verification

Although cisplatin CP [ cis -diamminedichloroplatinum II , CDDP], is potent anticancer medication use to treat a variety of tumors including testicular, ovarian, bladder, and lung Ibrahim et al.

Several recent studies recorded that the CP induces hepatotoxicity Abdellatief et al. Miller et al. Moreover, inflammation, apoptosis, and oxidative stress were mentioned as the most relevant pathways for CP toxicity Meng et al.

In the last decades, VIM is considered a mesenchymal marker for liver and kidney toxicity Matos et al. Moreover, CKs are known as cellular stress protein, specially CK18, which use as novel markers of the liver and kidney injuries Yang et al. L-carnitine LC is a natural nutrient, which synthesis from lysine and methionine essential amino acids.

LC is necessary for the production of ATP by β-oxidation of fatty acids in mitochondria Furuno et al. Therefore, LC can prevent mitochondrial oxidative stress induces mitochondria damage and apoptosis in different cell types Barhwal et al.

The major regulatory role of LC in antioxidant processes was discussed in various organs like heart, colon, retina, and brain Al-Majed et al. In addition, both histological alterations and immunohistochemical expressions of VIM and CK18 proteins were evaluated in all experimental groups.

Cisplatin was obtained from EIMC United Pharmaceuticals, Egypt. LC was obtained from MEPACO Company Inshas Elraml, Egypt. N-ethylmaleimide was obtained from Sigma Al-drich Co. All biochemical analysis kits were purchased from Biodiagnostics Company Dokki, Giza, Egypt.

The present study was carried out on a total number of 28 white Albino male rats weighed ± 5. Rats were obtained from the Laboratory Animal Center, Faculty of Veterinary Medicine, Benha University, Egypt.

They were acclimatized for two weeks prior to the experiment. The experimental design of the present study was ethically approved by the Ethics Review Committee of the Faculty of Veterinary Medicine, Benha University, Egypt Approval No. All rats received standard laboratory balanced commercial diet and water ad libitum.

In the present study, male albino rats were randomly assigned into 4 equal groups 7 rats each. Group I control , was administered saline orally the vehicle once daily for 30 consecutive days. Group III was served as CP toxic control and received saline orally once daily and a single dose of CP on the 27 th day of the experiment 7.

Group IV was received both LC and CP. The saline or LC was given orally at 10 AM along the experimental period 30 days. After 24 h from the end of the experiment, rats were anesthetized by isoflurane.

Blood samples from each rat were collected by puncturing retro-orbital plexus in sterilized dry centrifuge tubes and kept for 30 min at room temperature RT in a slanted position for blood coagulation before centrifugation at × g for 20 min to obtain serum.

The serum was preserved at °C until used for biochemical investigations. After blood collection, the animals of all groups were sacrificed by cervical decapitation then the liver and kidneys were excised from each rat and washed with physiological saline.

A gram specimen of each tissue was homogenized in 5 ml phosphate buffer pH 7. After homogenization, N-ethylmaleimide was added directly to prevent oxidation of GSH. Tissue homogenates were centrifuged at 1, × g for 20 min at 4°C.

The resulting supernatants were isolated and used in the assessment of the oxidative stress biomarkers in hepatic and renal tissues. All rats 28 and remnants of samples were buried in the strict hygienically controlled properly constructed burial pit.

The activities of alanine aminotransferase ALT , aspartate aminotransferase AST Reitman and Frankel, , and alkaline phosphatase ALP Tietz et al. While albumin and total protein were determined according to Doumas et al.

In addition, the serum levels of urea and creatinine were determined according to Coulombe and Favreau and Bartels et al. Tissue specimens were taken from the liver and kidney of rats in different groups.

Then, specimens were dehydrated in serial dilutions of alcohol, cleared in xylene and embedded in paraffin. Paraffin sections of 5 microns thickness were cut and collected on glass slides and stained by hematoxylin and eosin for histological examination Bancroft et al.

Liver and kidney paraffin sections of 5 microns thickness were cut and collected on positively charged slides for immunohistochemical localization of VIM and CK18 using a streptavidin-biotin complex ABC method. After, dewaxing, rehydration, and blocking endogenous peroxidase activity, the sections were heated at 90°C with citrate buffer pH 6 for 30 min.

The sections were then incubated with the primary antibodies rabbit monoclonal anti-vimentin and anti-cytokeratin 18, Abcam, Boston, the USA at dilution for 1 h at RT.

Next, sections were incubated with biotinylated donkey anti-mouse IgG Abcam, Boston, USA for 30 min at RT. The visualization of the immunoreactions was observed using a commercial ABC system recommended by the manufacturer Santa Cruz Biotech, CA, USA.

Then the slides were then subjected to diaminobenzene DAB as the chromogen and counterstained with hematoxylin.

The VIM and CK18 staining in both hepatic and renal tissues of all examined rats were evaluated blindly. At least 5 random high-power fields were checked at a magnification of X using Leica DM microscope. Staining features were scored semi-quantitatively according to Liu et al. Statistical analysis was performed using SPSS Version The significant differences between groups were evaluated by one-way ANOVA using the Duncan test as a post hoc.

Results were expressed as mean ± SEM. LC administration with CP restored these parameters towards the normal values Table 1. In the present study, there was substantially increased in MDA level along with a dramatic decrease in GSH and CAT in the liver and kidney tissues of CP-intoxicated rats.

Liver sections from control and LC treated rats exhibited normal hepatic histo-architecture. Hepatocytes organize in cords radiating from the central vein and separate by regular sinusoids Figures 1A, B.

Otherwise, CP treated rats revealed several histological changes like dilatation of the central vein and sinusoids, inflammatory cells aggregation, Kupffer cells proliferation Figure 1C , swelling of hepatocytes, hydropic degeneration Figure 1D , and fatty infiltration with signet ring appearance in some hepatocytes Figure 1E.

Figure 1 Histological sections of livers from all examined groups. A, B Control and LC groups showed normal hepatic histo-architecture. Hepatocytes organized in cords radiating from central vein CV and separated by regular sinusoids wide black arrow. C—E CP treated rats showed several histological changes.

C showed dilatation of the central vein CV and sinusoids wide black arrow , inflammatory cells aggregation IC , and kupffer cells proliferation thin arrow. D showed swelling of hepatocytes, hydropic degeneration hollow arrow.

E showed fatty infiltration with signet ring appearance in some hepatocytes hollow arrow. Kidney sections from both control and LC groups showed regular renal histo-architecture with normal renal corpuscles and renal tubules; proximal PCT and distal convoluted tubules DCT and collecting CT tubules Figures 2A, B.

In the CP group, many distinguishing histological changes were noted including excessive degenerative changes and desquamation of the tubular epithelia were observed Figures 2C—E with the presence of eosinophilic hyaline casts in some tubules Figures 2D, E.

Also, deformity of some glomeruli with the widening of glomerular space was identified Figure 2E as well as congestion of peritubular blood vessels and capillaries Figures 2C—E. Figure 2 Histological section of kidneys from all examined groups.

A, B Control and LC groups showed regular renal histo-architecture with normal renal corpuscles RC and renal tubules; proximal PCT distal convoluted tubules DCT and collecting tubules CT. Degenerative changes and desquamation of the tubular epithelia D , eosinophilic hyaline casts HC in some tubules, deformity of some golumeruli with widening of glomerular space wide black arrows and congestion of peritubular blood vessels and capillaries hollow arrows.

A summary of VIM and CK18 immunohistochemical expressions in the livers and kidneys of all examined groups was recorded Tables 3 , 4. Table 3 Summary of VIM and CK18 immunohistochemical expressions in the livers of all examined groups. Table 4 Summary of VIM and CK18 immunohistochemical expressions in the kidneys of all examined groups.

Both control and LC rats expressed weakly to moderate VIM mainly in the hepatic sinusoids and Kupffer cells, but the hepatocytes were VIM negative Figures 3A, B. Meanwhile, CP-injected rats showed overexpression of VIM in the blood sinusoids Figure 3C and an increased number of Kupffer cells Figures 3D, E as well as some hepatocytes labeled weak VIM Figure 3E.

Figure 3 Immunohistochemical staining of VIM in hepatic sections from all examined groups. A, B Control and LC groups showed weak to moderate hepatic sinusoids wide arrow and Kupffer cells thin arrow for VIM. C—E CP group revealed overexpression of VIM in blood sinusoids wide arrow , Kupffer cells thin arrows and some hepatocytes showed weak VIM hollow arrow.

In kidneys, VIM was expressed mainly in the glomeruli, some peritubular blood capillaries, and interstitial fibroblasts of all experimental groups Figure 4.

In both control and LC groups, the renal tubules did not express VIM protein but, the interstitial tissues and glomeruli showed weak and moderate VIM staining, respectively Figures 4A, B.

Figure 4 Immunohistochemical staining of VIM in renal sections from all examined groups. A, B Control and LC groups showed weak to moderate VIM staining in the interstitial tissues thin arrow , blood capillaries BC , and glomeruli G.

C CP group revealed moderate glomerular G and strong tubular RT and interstitial thin arrow VIM staining. Hepatocytes of both control and LC rats showed weak CK18 staining at the periphery of the cells giving reticular appearance Figures 5A, B.

CP group revealed strong, dense, and clumped CK18 staining in the hepatocytes surrounding the central veins, fat cells, and triad area Figures 5C—E. Figure 5 Immunohistochemical staining of CK18 in hepatic sections from all examined groups.

A, B Control and LC groups showed weak CK18 staining at the periphery of the hepatocytes in reticular pattern thin arrows. C—E CP group revealed strong, dense, and clumped CK18 staining in hepatocytes surrounding the central veins thin arrows , fat cells thin arrows , and triad area thin arrows.

However, CK18 was overexpressed in the epithelial cells of renal tubules mainly PCT and few DCT after injection of CP Figure 6C. Figure 6 Immunohistochemical staining of CK18 in renal sections from all examined groups.

C CP group revealed overexpression of CK18 in the epithelial cells of renal tubules mainly proximal convoluted PCT and few distal convoluted DCT tubules. Hepatic and renal toxicity is the most common dose-limiting side effects of CP-induced chemotherapy Neamatallah et al.

Reducing the potential side effects of CP by LC can be helpful during chemotherapy. Elevated activities of liver enzymes are known to be markers of cellular leakage and loss of functional integrity of hepatocytes because they are released into the bloodstream when the hepatocyte plasma membrane is impaired Jia et al.

In this work, CP-induced hepatotoxicity was evidenced by significant alternation in serum liver enzymes AST, ALT, and ALP. This result may be attributed to the metabolism of CP. Mohamed and Badawy reported CP is significantly taken up by the liver and accumulated in the hepatocyte, causing its damage leading to an increase of the liver enzymes activities.

In addition, CP elevates creatinine and urea levels, which are confirmed by Sadeghi et al. On the other hand, Cayir et al. Cisplatin administration produced a significant decrease in the total proteins and albumin, this result is supported by the result of Abuzinadah and Ahmad These results own to oxidative stress that is mediated through the generation of reactive oxygen species ROS such as superoxide anion and hydroxyl radical and depletion in plasma antioxidant levels Fadl et al.

So, our results are in harmony with several experimental and clinical studies suggesting that the oxidative stress through the formation of free radicals is one of the mechanisms of CP-induced hepato-renal toxicity Ibrahim et al.

On the other side, LC is a natural nutrient and necessary for the oxidation of fatty acid in the mitochondria to produce ATP Tunez et al.

So, it has antioxidant properties and plays protective roles against oxidative stress in various tissues, including liver and kidney Cayir et al. Also, LC can improve the antioxidant enzyme activity, including CAT and GSH, and reduces the MDA concentration in renal tissues in acute renal failure induced by myoglobinuric in rats Aydogdu et al.

These results were confirmed by the results of histopathology. The ability of LC to significantly improve liver and kidney biochemical parameters may be due to its antioxidant effect and its capability to act as a free radical scavenger, leading to the protection of membrane permeability Augustyniak and Skrzydlewska, LC prevents oxidative stress and exerts a protective role against mitochondrial toxic agents Barhwal et al.

Additionally, they reduce the harmful effects of free fatty acids by enabling β-oxidation Furuno et al. Several histological changes in the liver among CP treated group were noted as recently mentioned by Abuzinadah and Ahmad The central vein and sinusoidal dilatation and congestion are in accordance with Cagin et al.

Also, swelling of hepatocytes, hydropic degeneration, and prominence of Kupffer cells are demonstrated in similarity to El-Shitany and Eid and Neamatallah et al.

In addition, fatty infiltration with signet ring appearance in some hepatocytes was seen as noted by Omar et al. Otherwise, the pretreatment of CP treated rats with LC can potentially protect the liver against CP-induced histological changes and significantly improve and normalize liver histology that represents by almost normal hepatocytes and sinusoids, but with mild congested central vein with regression of the fatty changes.

These findings are similar to El-Shitany and Eid , indicating that LC can attenuate the hepatotoxic effect of CP Cayir et al. Like the recent finding of Abd El-Kader and Taha ; Abdel-Razek et al.

Moreover, the presence of eosinophilic hyaline casts in some renal tubules agrees with Abd El-Kader and Taha and Abdel-Razek et al. Additionally, the deformity of some glomeruli with a widening of glomerular spaces was detected in accordance with Abd El-Kader and Taha On the other hand, LC administration ameliorated the histological effects of CP on the kidney, but with mild histological findings evidenced by tubular injury in some renal tubules, and minimal interstitial congestion.

This finding confirmed that LC could attenuate the nephrotoxic effect of CP Yürekli et al. The current study focused on immunohistochemical localization of VIM and CK18 in hepato-renal specimens since VIM and CK18 expressions in the liver and kidney had provided a valuable insight into their microanatomy in both healthy and diseased conditions.

A co-expression of VIM and CK in areas of damaged tissues was reported Moll et al. Concerning VIM protein, it has been linked with several pathophysiological conditions such as cancer, rheumatoid arthritis, and HIV Danielsson et al.

The detectable VIM in hepatic sinusoids of the present study confirmed the report of Evans where VIM is widely expressed IF proteins in endothelial cells and fibroblasts. According to Wang et al. At the beginning of this decade, both Golbar et al. Moreover, Kupffer cells in the current study were VIM positive as mentioned by Sharifi et al.

After the injection of CP, an overexpression of VIM in the liver was demonstrated in similarity to the lipopolysaccharide intoxicated liver Lee et al. The numbers of VIM positive Kupffer cells were increased Golbar et al. As well as, sinusoidal VIM expression was increased in response to CP toxicity where HSCs are activated into myofibroblasts, which characterize by higher VIM expression and more secretion of the extracellular matrix so, they consider as the major contributor to hepatic fibrosis Shang et al.

In the normal and diseased kidney, VIM is abundantly present in glomerular mesangial and epithelial cells Gonlusen et al.

Our study revealed VIM expression in the glomeruli of all examined rats confirming the above-mentioned data. In addition, VIM was expressed in the interstitial blood vessels and fibroblasts of all examined rats that agree with Stefanovic et al.

It was interesting that the current results revealed undetectable VIM in the renal tubular epithelium of the control rats that agree with Skinnider et al. Otherwise, the overexpression of VIM in renal tubules and interstitial tissue of the CP group was noted may be attributed to glomerulonephritis or tubule-interstitial injury Gonlusen et al.

Cytokeratins of hepato-renal tissues increase in response to toxicants, oxidative stress, inflammation, and other damaging insults Toivola et al. Hepatocytes, as one of the epithelial cells of the liver, have been known to express CKs Ku et al.

The hepatocytes of both control and LC treated rats showed faint CK18 at the cell periphery forming reticular staining patterns that agree with Zatloukal et al.

Upon injury by CP, the intoxicated hepatocytes exhibited strong, dense, and clumped CK18 staining that agrees with Omary and Coulumbe Moreover, immunohistochemical overexpression of CK18 in hepatocellular carcinoma was noted Sawan, These findings point to the structural role of CK18 to hepatocytes providing them mechanical stability.

Another role of CK18 is a target and modulator of toxic stress Zatloukal et al. That confirmed CK levels as a predictor for hepatitis progression Yang et al.

Cytokeratins are often used as disease markers in renal pathology and experimental research Djudjaj et al. CK18 staining was stronger in the collecting ducts as mentioned by Sen et al.

Like Snider , our finding showed a pronounced overexpression of CK18 in the damaged renal tubules in CP treated group indicating that CK18 was upregulated by tubular injury. Therefore, CK18 can be used as a marker and regulator of renal tubular epithelial injury Djudjaj et al.

It was noteworthy to record that the pretreatment of LC could decrease expressions of VIM and CK18 in hepato-renal tissues compared with CP group indicating the ameliorative role of LC against CP toxicity, especially in restoring the organization of IFs.

Cisplatin induced hepato-renal toxicity associated with oxidative damage, lipid peroxidation, histological changes, and disorganization of the cytoskeleton IFs; VIM and CK Therefore, this study suggests LC as a supplement for cancer patients under CP treatment.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. The animal study was reviewed and approved by Faculty of Veterinary Medicine, Benha University, Egypt.

All authors contributed equally to this article. SA and MA-D funding acquisition and project administration and assisted in writing and editing the manuscript with other authors. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Abd El-Kader, M. Comparative nephroprotective effects of curcumin and etoricoxib against cisplatin-induced acute kidney injury in rats. Acta Histochem. doi: PubMed Abstract CrossRef Full Text Google Scholar. Abdel-Daim, M. Nephroprotective efficacy of ceftriaxone against cisplatin-induced subchronic renal fibrosis in rats.

CrossRef Full Text Google Scholar. Impact of garlic Allium sativum oil on cisplatin-induced hepatorenal biochemical and histopathological alterations in rats. Total Sci.

Abdellatief, S. Ameliorative effect of parsley oil on cisplatin-induced hepato-cardiotoxicity: a biochemical, histopathological, and immunohistochemical study. Abdel-Razek, E. Benzbromarone mitigates cisplatin nephrotoxicity involving enhanced peroxisome proliferator-activated receptor-alpha PPAR-α expression.

Life Sci. Abo-Elmaaty, A. The protective efficacy of vitamin E and cod liver oil against cisplatin-induced acute kidney injury in rats.

Aboubakr, M. l-Carnitine and vitamin E ameliorate cardiotoxicity induced by tilmicosin in rats. Abuzinadah, M. Pharmacological studies on the efficacy of a thymoquinone-containing novel polyherbal formulation against cisplatin-induced hepatorenal toxicity in rats.

Food Biochem. Adeyemi, O. Citrullus colocynthis Linn. Fruit extract ameliorates cisplatin-induced hepato-renal toxicity in rats. Aebi, H. Catalase in vitro.

Aiad, H. The role of CK7, Ki, CD34 and vimentin in the differentiation between biliary atresia and idiopathic neonatal hepatitis in Egyptian cholestatic neonates.

Acta Pathol. Al-Majed, A. Propionyl-L-carnitine prevents the progression of cisplatin-induced cardiomyopathy in a carnitine-depleted rat model. Carnitine has been used as an energy supplement but the roles in improving health and delaying aging remain unclear.

Here we show in C. elegans that L-carnitine improves recovery from oxidative stress and extends lifespan. L-carnitine promotes recovery from oxidative stress induced by paraquat or juglone and improves mobility and survival in response to H 2 O 2 and human amyloid Aβ toxicity. L-carnitine also alleviates the oxidative stress during aging, resulting in moderate but significant lifespan extension, which was dependent on SKN-1 and DAF Long-lived worms with germline loss glp-1 or reduced insulin receptor activity daf-2 recover from aging-associated oxidative stress faster than wild-type controls and their long lifespans were not further increased by L-carnitine.

A new gene, T08B1. Together, our study suggests an important role of L-carnitine in oxidative stress recovery that might be important for healthy aging in humans. Zheng-Lin Ou zhenglinou csu. Navigate Home Editorial Board Information For Authors Advance Online Publications Current Issue Archive Scientific Integrity Publication Ethics and Publication Malpractice Statements Contact Special Collections Podcast News Room Interviews with Outstanding Authors.

L-carnitine and oxidative stress -

These results were confirmed by the results of histopathology. The ability of LC to significantly improve liver and kidney biochemical parameters may be due to its antioxidant effect and its capability to act as a free radical scavenger, leading to the protection of membrane permeability Augustyniak and Skrzydlewska, LC prevents oxidative stress and exerts a protective role against mitochondrial toxic agents Barhwal et al.

Additionally, they reduce the harmful effects of free fatty acids by enabling β-oxidation Furuno et al. Several histological changes in the liver among CP treated group were noted as recently mentioned by Abuzinadah and Ahmad The central vein and sinusoidal dilatation and congestion are in accordance with Cagin et al.

Also, swelling of hepatocytes, hydropic degeneration, and prominence of Kupffer cells are demonstrated in similarity to El-Shitany and Eid and Neamatallah et al. In addition, fatty infiltration with signet ring appearance in some hepatocytes was seen as noted by Omar et al. Otherwise, the pretreatment of CP treated rats with LC can potentially protect the liver against CP-induced histological changes and significantly improve and normalize liver histology that represents by almost normal hepatocytes and sinusoids, but with mild congested central vein with regression of the fatty changes.

These findings are similar to El-Shitany and Eid , indicating that LC can attenuate the hepatotoxic effect of CP Cayir et al. Like the recent finding of Abd El-Kader and Taha ; Abdel-Razek et al. Moreover, the presence of eosinophilic hyaline casts in some renal tubules agrees with Abd El-Kader and Taha and Abdel-Razek et al.

Additionally, the deformity of some glomeruli with a widening of glomerular spaces was detected in accordance with Abd El-Kader and Taha On the other hand, LC administration ameliorated the histological effects of CP on the kidney, but with mild histological findings evidenced by tubular injury in some renal tubules, and minimal interstitial congestion.

This finding confirmed that LC could attenuate the nephrotoxic effect of CP Yürekli et al. The current study focused on immunohistochemical localization of VIM and CK18 in hepato-renal specimens since VIM and CK18 expressions in the liver and kidney had provided a valuable insight into their microanatomy in both healthy and diseased conditions.

A co-expression of VIM and CK in areas of damaged tissues was reported Moll et al. Concerning VIM protein, it has been linked with several pathophysiological conditions such as cancer, rheumatoid arthritis, and HIV Danielsson et al.

The detectable VIM in hepatic sinusoids of the present study confirmed the report of Evans where VIM is widely expressed IF proteins in endothelial cells and fibroblasts.

According to Wang et al. At the beginning of this decade, both Golbar et al. Moreover, Kupffer cells in the current study were VIM positive as mentioned by Sharifi et al. After the injection of CP, an overexpression of VIM in the liver was demonstrated in similarity to the lipopolysaccharide intoxicated liver Lee et al.

The numbers of VIM positive Kupffer cells were increased Golbar et al. As well as, sinusoidal VIM expression was increased in response to CP toxicity where HSCs are activated into myofibroblasts, which characterize by higher VIM expression and more secretion of the extracellular matrix so, they consider as the major contributor to hepatic fibrosis Shang et al.

In the normal and diseased kidney, VIM is abundantly present in glomerular mesangial and epithelial cells Gonlusen et al. Our study revealed VIM expression in the glomeruli of all examined rats confirming the above-mentioned data.

In addition, VIM was expressed in the interstitial blood vessels and fibroblasts of all examined rats that agree with Stefanovic et al. It was interesting that the current results revealed undetectable VIM in the renal tubular epithelium of the control rats that agree with Skinnider et al.

Otherwise, the overexpression of VIM in renal tubules and interstitial tissue of the CP group was noted may be attributed to glomerulonephritis or tubule-interstitial injury Gonlusen et al.

Cytokeratins of hepato-renal tissues increase in response to toxicants, oxidative stress, inflammation, and other damaging insults Toivola et al. Hepatocytes, as one of the epithelial cells of the liver, have been known to express CKs Ku et al.

The hepatocytes of both control and LC treated rats showed faint CK18 at the cell periphery forming reticular staining patterns that agree with Zatloukal et al.

Upon injury by CP, the intoxicated hepatocytes exhibited strong, dense, and clumped CK18 staining that agrees with Omary and Coulumbe Moreover, immunohistochemical overexpression of CK18 in hepatocellular carcinoma was noted Sawan, These findings point to the structural role of CK18 to hepatocytes providing them mechanical stability.

Another role of CK18 is a target and modulator of toxic stress Zatloukal et al. That confirmed CK levels as a predictor for hepatitis progression Yang et al. Cytokeratins are often used as disease markers in renal pathology and experimental research Djudjaj et al.

CK18 staining was stronger in the collecting ducts as mentioned by Sen et al. Like Snider , our finding showed a pronounced overexpression of CK18 in the damaged renal tubules in CP treated group indicating that CK18 was upregulated by tubular injury.

Therefore, CK18 can be used as a marker and regulator of renal tubular epithelial injury Djudjaj et al. It was noteworthy to record that the pretreatment of LC could decrease expressions of VIM and CK18 in hepato-renal tissues compared with CP group indicating the ameliorative role of LC against CP toxicity, especially in restoring the organization of IFs.

Cisplatin induced hepato-renal toxicity associated with oxidative damage, lipid peroxidation, histological changes, and disorganization of the cytoskeleton IFs; VIM and CK Therefore, this study suggests LC as a supplement for cancer patients under CP treatment. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The animal study was reviewed and approved by Faculty of Veterinary Medicine, Benha University, Egypt. All authors contributed equally to this article. SA and MA-D funding acquisition and project administration and assisted in writing and editing the manuscript with other authors.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Abd El-Kader, M. Comparative nephroprotective effects of curcumin and etoricoxib against cisplatin-induced acute kidney injury in rats. Acta Histochem. doi: PubMed Abstract CrossRef Full Text Google Scholar. Abdel-Daim, M. Nephroprotective efficacy of ceftriaxone against cisplatin-induced subchronic renal fibrosis in rats.

CrossRef Full Text Google Scholar. Impact of garlic Allium sativum oil on cisplatin-induced hepatorenal biochemical and histopathological alterations in rats.

Total Sci. Abdellatief, S. Ameliorative effect of parsley oil on cisplatin-induced hepato-cardiotoxicity: a biochemical, histopathological, and immunohistochemical study.

Abdel-Razek, E. Benzbromarone mitigates cisplatin nephrotoxicity involving enhanced peroxisome proliferator-activated receptor-alpha PPAR-α expression. Life Sci. Abo-Elmaaty, A. The protective efficacy of vitamin E and cod liver oil against cisplatin-induced acute kidney injury in rats.

Aboubakr, M. l-Carnitine and vitamin E ameliorate cardiotoxicity induced by tilmicosin in rats. Abuzinadah, M. Pharmacological studies on the efficacy of a thymoquinone-containing novel polyherbal formulation against cisplatin-induced hepatorenal toxicity in rats.

Food Biochem. Adeyemi, O. Citrullus colocynthis Linn. Fruit extract ameliorates cisplatin-induced hepato-renal toxicity in rats. Aebi, H. Catalase in vitro. Aiad, H. The role of CK7, Ki, CD34 and vimentin in the differentiation between biliary atresia and idiopathic neonatal hepatitis in Egyptian cholestatic neonates.

Acta Pathol. Al-Majed, A. Propionyl-L-carnitine prevents the progression of cisplatin-induced cardiomyopathy in a carnitine-depleted rat model.

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Neuroreport — Yang MS, Chan HW, Yu LC Glutathione peroxidase and glutathione reductase activities are partially responsible for determining the susceptibility of cells to oxidative stress. Toxicology — Campese VM, Sindhu RK, Ye S, Bay Y, Vaziri ND, Jabbari B Regional expression of NO synthase, NAD P H oxidase and superoxide dismutase in the rat brain.

Brain Res — Beard JL, Connor JR, Jones BC Iron in the brain. Nutr Rev — Jones LL, McDonald DA, Borum PR Acylcarnitines: role in brain. Prog Lipid Res — Mc Guire PJ, Parikh A, Diaz GA Profiling of oxidative stress in patients with inborn errors of metabolism. Download references. This work was supported by research grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq , Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES , and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul FAPERGS.

Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos, , Porto Alegre, , Rio Grande do Sul, Brazil. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Rua Ramiro Barcelos, , , Porto Alegre, Rio Grande do Sul, Brazil.

Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, , Porto Alegre, , Rio Grande do Sul, Brazil. Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, , , Porto Alegre, Rio Grande do Sul, Brazil.

You can also search for this author in PubMed Google Scholar. Correspondence to Carlos Severo Dutra-Filho. Reprints and permissions. Mescka, C. et al. L-carnitine Prevents Oxidative Stress in the Brains of Rats Subjected to a Chemically Induced Chronic Model of MSUD. Mol Neurobiol 53 , —

Essential nutrients for tennis players CP is one of the most sstress medications in cancer treatment and has some adverse effects such Herbal remedies for skin care hepatotoxicity oxidatiev nephrotoxicity. Twenty-eight rats were divided into four groups L-carnitine and oxidative stress rats each. Group Ans received saline orally once daily and a single dose of CP on the 27th day of the experiment [7. Group IV received both LC and CP. In addition, CP induced a dramatic increase in the Malondialdehyde MDA level along with a substantial decrease in reduced glutathione GSH and catalase CAT in the hepato-renal tissues. Histologically, both liver and kidney of the CP treated group revealed marked degenerative changes.

Author: Juzil

2 thoughts on “L-carnitine and oxidative stress

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