title: Ascorbic acid supplementation down-regulates the alcohol induced oxidative stress, hepatic stellate cell activation, cytotoxicity and mRNA levels of selected fibrotic genes in guinea pigs.
abstract: Both oxidative stress and endotoxins mediated immunological reactions play a major role in the progression of alcoholic hepatic fibrosis. Ascorbic acid has been reported to reduce alcohol-induced toxicity and ascorbic acid levels are reduced in alcoholics. Hence, we investigated the hepatoprotective action of ascorbic acid in the reversal of alcohol-induced hepatic fibrosis in male guinea pigs (n = 36), and it was compared with the animals abstenting from alcohol treatment. In comparison with the alcohol abstention group, there was a reduction in the activities of toxicity markers and levels of lipid and protein peroxidation products, expression of α-SMA, caspase-3 activity and mRNA levels of CYP2E1, TGF-β(1), TNF-α and α(1)(I) collagen in liver of the ascorbic acid-supplemented group. The ascorbic acid content in liver was significantly reduced in the alcohol-treated guinea pigs. But it was reversed to normal level in the ascorbic acid-supplemented group. The anti-fibrotic action of ascorbic acid in the rapid regression of alcoholic liver fibrosis may be attributed to decrease in the oxidative stress, hepatic stellate cells activation, cytotoxicity and mRNA expression of fibrotic genes CYP2E1, TGF-β(1), TNF-α and α(1) (I) collagen in hepatic tissues.
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, Kerala, India.
authors.forename: P A
authors.initials: PA
authors.lastname: Abhilash
authors.forename: R
authors.initials: R
authors.lastname: Harikrishnan
authors.forename: M
authors.initials: M
authors.lastname: Indira
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000493:pharmacokinetics / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D016166:Free Radical Scavengers / Q000493:pharmacokinetics / Q000494:pharmacology*; D006168:Guinea Pigs; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D016166:Free Radical Scavengers; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D019392:Cytochrome P-450 CYP2E1; D053148:Caspase 3; D001205:Ascorbic Acid