Thioacetamide-induced hepatic damage in a rat nutritional model of steatohepatitis.
BACKGROUND
Nonalcoholic steatohepatitis is most often attributed to the effects of obesity, hyperlipidemia, diabetes mellitus and drugs. It is still unknown whether livers with steatohepatitis are more vulnerable to toxic damage.


OBJECTIVE
To determine the effect of the hepatotoxicant thioacetamide in a rat nutritional model of hepatic steatohepatitis.


METHODS
Fatty liver was induced in rats by placing them on a methionine-choline deficient diet for one month. Thioacetamide was administered by 3 consecutive intraperitoneal injections (300 mg/kg) at 24 h intervals.


RESULTS
Following treatment with thioacetamide, the elevated serum levels of liver enzymes and blood ammonia, liver necrotic inflammation and the survival rate after 48 h were not different between rats with normal or fatty liver. However, those parameters were significantly worse when fatty liver regressed after return to normal diet for one month (p < 0.01). Western blot analysis of hepatic extracts revealed no difference in cytochrome P4502E1 levels between fatty livers and fatty livers after regression, suggesting that the enhanced hepatotoxicity after regression of fatty liver could not be attributed to increased cytochrome P4502E1.


CONCLUSIONS
In a nutritional model of steatohepatitis, rats with fatty liver were not more vulnerable than normal rats to liver damage induced by thioacetamide. However, liver damage was significantly more severe in rats with fatty livers after one month regression of steatosis.
Department of Gastroenterology, The E. Wolfson Medical Center, Holon, Israel.
Yona
Y
Avni
Haim
H
Shirin
Hussein
H
Aeed
Zipora
Z
Matas
Mark
M
Shahmurov
Shlomo
S
Birkenfeld
Rafael
R
Bruck
D000818:Animals; D002794:Choline / Q000502:physiology; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology*; D006505:Hepatitis / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000172:deficiency; D016328:NF-kappa B; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide / Q000008:administration & dosage / Q000633:toxicity*
D016328:NF-kappa B; D013853:Thioacetamide; D008715:Methionine; D019392:Cytochrome P-450 CYP2E1; D002794:Choline