Insulin resistance induced by high-fructose diet potentiates carbon tetrachloride hepatotoxicity.
Insulin resistance (IR) is recognized as a contributory factor for a variety of liver diseases. The present study investigates the susceptibility of liver to the toxic actions of carbon tetrachloride (CCl(4)) in a rat model of IR, induced by feeding a high-fructose diet (60 g/100 g) for 30 days. A sub-lethal dose of CCl(4) (2 mL/kg intraperitoneally [i.p.], in corn oil) was administered and the outcome of hepatotoxicity was assessed at 0 hour and at 6, 12, 24 and 36 hours after CCl(4) administration. After 30 days of fructose feeding, the rats showed IR, decline in liver antioxidant status and rise in lipid peroxidation. Liver dysfunction in fructose-fed rats was evident from a rise in transaminases, total bilirubin and a decrease in albumin/globulin ratio in plasma and decreases in nitrite, arginase and increase in protein carbonyl and nitrosothiol content in liver. Increased staining for 3-nitro tyrosine (3-NT) antibody was observed in fructose-fed rat liver as compared to control. CCl(4) (2 mL/kg) caused 100% mortality in fructose-fed rats within 48 hours, while no death of animals occurred in control. CCl(4) caused liver damage in both control and fructose-fed rats. Time-based studies showed that progressive liver injury occurred only in fructose-fed rats from 0, 6, 12, 24 hours, with a peak at 36 hours. In control diet-fed rats, the extent of damage was maximum at 24 hours, which declined at 36 hours. Thus, the toxic effects of CCl(4) are potentiated due to compromised liver function in the setting of IR.
Pooranaperundevi
M
M
Department of Biochemistry and Biotechnology, Annamalai University, Tamil Nadu, India.
Sumiyabanu
M S
MS
Viswanathan
P
P
Sundarapandiyan
R
R
Anuradha
C V
CV
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002252:Carbon Tetrachloride Poisoning / Q000097:blood / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology* / Q000378:metabolism*; D004357:Drug Synergism; D005632:Fructose / Q000008:administration & dosage / Q000633:toxicity*; D006651:Histocytochemistry; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology; D008297:Male; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; D005632:Fructose; D002251:Carbon Tetrachloride