Sensitivity of several serum enzymes for the detection of thioacetamide-, dimethylnitrosamine- and diethanolamine-induced liver damage in rats

Abstract

Studies were conducted to compare the sensitivity of different methods of assessing liver damage and to identify enzymes in serum which respond quantitatively to low doses of hepatotoxins. Male adult Sprague-Dawley rats were killed 18 hr after single po doses of thioacetamide (TA), dimethylnitrosamine (DMN) or diethanolamine (DEA). Serum sorbitol dehydrogenase activity increased when 9.4 mg TA/kg or 5.1 mg DMN/kg was given and the activity of 7 other enzymes in serum increased when larger doses were given. Serum concentrations of arginine decreased and ornithine increased when 25.4 mg TA/kg or 13.7 mg DMN/kg was given. When 800 mg/kg of diethanolamine (DEA) was given the serum activity of sorbitol dehydrogenase, isocitrate dehydrogenase, fructose-1-phosphate aldolase, glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase and malic dehydrogenase increased. When the dose was increased to 1600 mg/kg the serum activity of ornithine carbamyl transferase, glutamic dehydrogenase, fructose-1,6-phosphate aldolase and lactic dehydrogenase increased. Serum concentrations of urea increased and arginine decreased when 800 mg DEA/kg was given. Activities of several enzymes were dose-dependent. Minimal morphological changes were seen in liver sections at dosage levels of each compound below those required to produce changes in serum enzyme activity. Sorbitol dehydrogenase was the most sensitive serum parameter studied.