The effect of diurnal rhythms on the hepatotoxicity of thioacetamide in male and female rats.

Single 200 mg/Kg body weight i.p. injections of thioacetamide administered to litter mate male and female rats at 09.00, 13.00, 17.00 and 21.00 h caused body weight losses, elevated plasma glutamate pyruvate transaminase (GPT) levels, decreases in hepatic glycogen, zone 3-specific necrosis and leucocyte infiltration. All of these changes were more marked in males. The effects of thioacetamide on females were more severe at later injection times while no diurnal variations were apparent in males. Decreases in hepatic glycogen were most obvious in necrotic perivenous hepatocytes and correlated with increases in active glycogen phosphorylase which were probably caused by raised cytosolic calcium concentrations resulting from thioacetamide induced damage to cell membranes.