Serum enzyme activities and hepatic triglyceride levels in acute and subacute acetaminophen-treated rats

Abstract

The dose- and time-related hepatotoxic effects of acetaminophen were investigated in rats using biochemical parameters as indices of hepatotoxicity supplemented by the histophatological examination of the livers. The acute or subacute (twice daily for 7 days) administration of 0.25 g/kg acetaminophen did not produce any noticeable heptocellular damage. On the other hand, dose-dependent elevations in serum enzyme glutamic-oxaloacetic transminase (GOT), glutamic-pyruvic transaminase (GPT) and sorbitol dehydrogenase (SDH) activities and hepatic triglyceride (TG)_levels were observed following the administration of single doses of 0.5 and 1 g/kg acetominophen. Maximal hepatic damage occured 12–18 h after acute dosing, while the hepatic function returned to control levels by 48–72 h. In contrast with the acutely treated rats, the serum enzyme activities and the hepatic TG levels remained unchanged following 7-day treatment with 0.5 or 1 g/kg acetomiophen. Also, histopathologically the degree of acetaminophpen-induced hepatic necrosis was found to be far lee extensive in rats given 0.5 to 1 g/kg acetiminophen twice daily for upt to one week, as compared with the animals sacrified 18 h after administering single equivalent doses of this drug. The results suggest that the function in intensity of acetaminophen-induced hepatotoxicity becomes less severe after repeated exposure to this hepatotoxin.