title: Ascorbic acid is superior to silymarin in the recovery of ethanol-induced inflammatory reactions in hepatocytes of guinea pigs.
abstract: Both oxidative stress and inflammatory reactions play a major role in alcoholic liver fibrosis. We evaluated the efficacy of ascorbic acid (AA) and silymarin in the regression of alcohol-induced inflammation in hepatocytes of guinea pigs (Cavia porcellus). Animals were administered with ethanol at a daily dose of 4 g/kg body weight (b.wt) for 90 days. On the ninety-first day, ethanol administration was stopped and animals were divided into alcohol abstention group and silymarin- (25 mg/100 g b.wt) and AA- (25 mg/100 g b.wt) supplemented groups and maintained for 30 days. There was a significant increase in the activities of alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase in the serum of the ethanol group. The intracellular reactive oxygen species (ROS) and expressions of cytochrome P4502E1 and nuclear factor κB1, tumor necrosis factor-α, and transforming growth factor-β(1) in hepatocytes were significantly increased in ethanol group. The fibrotic markers α-smooth muscle actin and α(1)(I) collagen and activity of cytotoxicity marker caspase-3 were significantly increased and AA content was significantly reduced in hepatocytes of alcohol-treated guinea pigs. But the AA and silymarin supplementation significantly reduced these changes in comparison with alcohol abstention group. AA could induce greater reduction of inflammatory and fibrotic markers in hepatocytes than silymarin. This indicates that AA is superior to silymarin in inhibiting intracellular ROS generation and thereby reducing the ethanol-induced inflammation in hepatocytes.
authors: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, Kerala, India.
authors: P A
authors: PA
authors: Abhilash
authors: R
authors: R
authors: Harikrishnan
authors: M
authors: M
authors: Indira
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage; D015870:Gene Expression; D006168:Guinea Pigs; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D012838:Silymarin / Q000494:pharmacology*; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000199:Actins; D000975:Antioxidants; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D016328:NF-kappa B; D020011:Protective Agents; D017382:Reactive Oxygen Species; D012838:Silymarin; D016212:Transforming Growth Factor beta; D000431:Ethanol; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C025619:steroid 16-beta-hydroxylase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001205:Ascorbic Acid
references: J Basic Clin Physiol Pharmacol. 2010;21(4):277-94
references: 21305846
references: Comp Biochem Physiol C Toxicol Pharmacol. 2003 Mar;134(3):397-401
references: 12643986
references: J Physiol Biochem. 2013 Jun;69(2):227-37
references: 22893526
references: Alcohol Clin Exp Res. 2005 Nov;29(11 Suppl):180S-8S
references: 16344606
references: Indian J Pharmacol. 2010 Apr;42(2):99-104
references: 20711375
references: Annu Rev Pharmacol Toxicol. 2004;44:27-42
references: 14744237
references: Cell Res. 2011 Jan;21(1):159-68
references: 21187858
references: Toxicol Sci. 2004 Jun;79(2):233-41
references: 15056802
references: Adv Anat Embryol Cell Biol. 2001;161:III-XIII, 1-151
references: 11729749
references: Alcohol Clin Exp Res. 1994 Oct;18(5):1280-5
references: 7847620
references: Hepatology. 1996 Jun;23(6):1468-75
references: 8675166
references: Methods Cell Biol. 1976;13:29-83
references: 177845
references: Alcohol Alcohol. 1985;20(2):89-124
references: 4052163
references: J Gastroenterol Hepatol. 1997 Oct;12(9-10):S272-82
references: 9407347
references: Hepatol Res. 2004 Dec;30(4):193-198
references: 15589125
references: Phytother Res. 2002 Mar;16 Suppl 1:S78-80
references: 11933147
references: Ann N Y Acad Sci. 1992 Sep 30;669:7-20
references: 1444060
references: Arch Biochem Biophys. 1982 Jan;213(1):200-31
references: 7036906
references: Nat Rev Gastroenterol Hepatol. 2011 Feb;8(2):108-18
references: 21293511
references: J Submicrosc Cytol Pathol. 1992 Apr;24(2):193-203
references: 1600511
references: J Hepatol. 2001 Aug;35(2):297-306
references: 11580156
references: Iran J Basic Med Sci. 2011 Jul;14(4):308-17
references: 23492971
references: Am J Physiol Gastrointest Liver Physiol. 2004 Nov;287(5):G1078-85
references: 15475485
references: Gastroenterology. 2004 May;126(5):1387-99
references: 15131799
references: Arch Biochem Biophys. 1993 Jul;304(1):209-18
references: 8323286
references: Hepatology. 2007 Aug;46(2):590-7
references: 17661407
references: Toxicol Lett. 1999 Feb 22;104(3):221-9
references: 10079057
references: Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998 Feb;119(2):125-9
references: 9669080
references: Clin Chem. 1969 Feb;15(2):124-36
references: 5773262
references: Redox Rep. 2012;17(2):72-9
references: 22564350
references: Indian J Biochem Biophys. 2006 Oct;43(5):306-11
references: 17133738
references: Hepatogastroenterology. 1997 Sep-Oct;44(17):1360-6
references: 9356856
references: J Clin Invest. 2005 Feb;115(2):209-18
references: 15690074
references: Am J Psychiatry. 1998 Jun;155(6):726-32
references: 9619143
references: Hepatology. 1998 Jun;27(6):1632-42
references: 9620337
references: Hum Mol Genet. 2008 Apr 1;17(7):963-70
references: 18079108
references: Clin Liver Dis. 2003 May;7(2):351-67
references: 12879988
references: Hepatology. 2008 May;47(5):1483-94
references: 18393316
references: Alcohol. 2007 Dec;41(8):587-9
references: 17980998
references: Proc Soc Exp Biol Med. 2000 Sep;224(4):302-8
references: 10964266
references: Gastroenterology. 1997 Mar;112(3):943-51
references: 9041257
references: Int J Clin Pharmacol Ther. 2002 Jan;40(1):2-8
references: 11841050
references: Dig Dis Sci. 2005 Oct;50(10):1807-12
references: 16187178
references: J Immunol. 1998 Apr 1;160(7):3480-6
references: 9531309
references: Alcohol Alcohol. 1994 Sep;29(5):513-22
references: 7811335
references: Hepatology. 2010 Apr;51(4):1438-44
references: 20209607
references: Res Commun Chem Pathol Pharmacol. 1994 Apr;84(1):63-72
references: 8042010
references: Free Radic Biol Med. 1994 Apr;16(4):417-26
references: 8005526
references: Chem Biol Interact. 1992 May;82(3):243-93
references: 1318789
references: Anal Biochem. 1987 Apr;162(1):156-9
references: 2440339