Effect of SKF525-A on the glutathione-conjugating enzyme system and on liver toxicity

SKF525-A given intraperitoneally (50 mg/kg body weight) to Sprague-Dawley rats in a single dose promoted a significant reduction in cytosolic glutathione S-transferase (GST) activities 0.5 and 1 h after injection. There was no decrease in liver non-protein sulfhydryls (NPSH) 0.5, 1 and 24 h after injection. Serum activities of glutamic pyruvic transaminase (GPT), sorbitol dehydrogenase (SDH), glutamic oxaloacetic transaminase (GOT) and glutamate dehydrogenase (GLDH) increased 1.8-, 2.9-, 3.8- and 41.2-fold respectively 8 h after injection, and the increased serum enzyme activities were maintained for up to 24 h. On the basis of these results, SKF525-A-induced blood manifestations of liver toxicity and decrease in GST activities may be regarded as confusing factors in the evaluation of the oxidative metabolism of compounds in Sprague-Dawley rats.