Insulin resistance induced by a high-fructose diet potentiates thioacetamide hepatotoxicity.
BACKGROUND
Insulin resistance (IR) is recognised as an aetiopathogenic factor for a variety of liver diseases. This study investigated the susceptibility of the liver to the toxic actions of thioacetamide (TA) in a rat model of IR, induced by feeding the rats a high-fructose diet (60 g/100 g) for 30 days.


METHODS
Hepatic function and damage were assessed at 0 hour and at 6, 12, 24 and 36 hours after a sublethal dose of TA (300 mg/kg intraperitoneally) was administered.


RESULTS
After 30 days of fructose feeding, the rats showed IR, a decline in their liver antioxidant status and a rise in lipid peroxidation. Liver dysfunction in fructose-fed rats was evident from a rise in transaminase and total bilirubin, a decrease in the albumin/globulin ratio in plasma, a decrease in nitrite and arginase, and an increase in protein carbonyl and nitrosothiol content in the liver. Increased staining for the 3-nitrotyrosine antibody was observed in the fructose-fed rat livers as compared to the controls. TA (300 mg/kg) caused 80 percent mortality in fructose-fed rats within 48 hours, while no death occurred among the controls.


CONCLUSIONS
Fructose-fed rats suffered from liver dysfunction and damage. TA caused liver injury in both control and fructose-fed rats. Time-based studies showed that progressive liver injury occurred only in rats that were fructose-fed from 6, 12 and 24 hours after TA administration, with a peak at 36 hours. In control diet-fed rats, the extent of damage was maximal at 24 hours, and declined at 36 hours. Thus, the toxic effects of TA are potentiated due to compromised liver function in the setting of IR.
Pooranaperundevi
M
M
Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar 608 002, Tamil Nadu, India.
Sumiyabanu
M S
MS
Viswanathan
P
P
Sundarapandiyan
R
R
Anuradha
C V
CV
D000418:Albumins / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001119:Arginase / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D007333:Insulin Resistance; D015227:Lipid Peroxidation; D008107:Liver Diseases / Q000209:etiology* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013549:Sweetening Agents / Q000008:administration & dosage / Q000009:adverse effects*; D013853:Thioacetamide / Q000633:toxicity*
D000418:Albumins; D000975:Antioxidants; D004040:Dietary Carbohydrates; D009573:Nitrites; D013549:Sweetening Agents; D013853:Thioacetamide; D005632:Fructose; D019392:Cytochrome P-450 CYP2E1; D001119:Arginase; D001663:Bilirubin