title: Sensitivity difference to hepatotoxicity of cocaine in spontaneously hypertensive and Wistar Kyoto rats.
abstract: Experiments were conducted to determine the hepatic damage of cocaine in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats in terms of serum glutamic-oxaloacetic transaminase (SGOT) activity, liver weight/body weight ratio and hepatic microsomal enzyme activity, i.e., N-demethylase activity or UDP-glucuronyltransferase (GT) activity. In subacute experiments, 2, 4 and 10 daily cocaine treatments elevated the level of SGOT activity and reduced the liver weight/body weight ratio in SHR rats. The ethylmorphine N-demethylase activity and the cocaine N-demethylase activity in SHR rats were significantly greater (31% and 26%, respectively) than those in WKY rats. Ten daily treatments with cocaine diminished the ethyl morphine N-demethylase activity and the cocaine N-demethylase activity in SHR and WKY rats. However, attenuation of 4-nitrophenol GT activity was only observed in SHR rats. In acute experiments, a single dose of cocaine, 40 mg/kg, elevated the SGOT activity in SHR rats and reduced the 4-nitrophenol GT activity in SHR rats, but it did not affect the activities of SGOT and 4-nitrophenol GT in WKY rats. A higher dose of cocaine, 60 mg/kg, elevated the SGOT activity and reduced cocaine N-demethylase activity and 4-nitrophenol GT activity in both SHR and WKY rats. The present studies suggest that N-demethylation of cocaine plays an important role in the hepatotoxicity of cocaine in animals.
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001711:Biotransformation; D003042:Cocaine / Q000378:metabolism / Q000633:toxicity*; D014453:Glucuronosyltransferase / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
chemical_list: D010089:Oxidoreductases, N-Demethylating; D014453:Glucuronosyltransferase; D001219:Aspartate Aminotransferases; D003042:Cocaine