Vanadate-induced toxicity towards isolated perfused rat livers: the role of lipid peroxidation.

摘要: Abstract The toxic potential of sodium ortho vanadate towards isolated perfused rat livers was investigated at a dose 2 mmol/l. In from fasted rats, led to release cytosolic (glutamate-pyruvate-transaminase (GPT) and lactate dehydrogenase (LDH)) mitochondrial (glutamate (GLDH)) enzymes, an accumulation calcium in the liver, marked depletion hepatic glutathione enhanced it into perfusate, as well augmented formation thiobarbituric acid-reactive material by liver. Furthermore, inhibition oxygen consumption observed. Vanadate-induced vasoconstriction resulted progressive decrease perfusate flow rate. Control experiments with similarly reduced rates comparable reduction consumption. GPT LDH were also evident, though lesser extent than presence vanadate, but no increase GLDH release, tissue content or TBA-reactive liver Thus, indirect effects due rate contribute only partly hepatotoxicity do not affect integrity. Omission did prevent hepatotoxic responses although less present treated control organs, indicating that influx is involved vanadate-induced intact organ, contrast hepatocytes [13]. Feeding animals, resulting activation anaerobic energy conservation reactions, strongly attenuated energetic status main target vanadate. Superoxide dismutase rats while allopurinol deferrioxamine inhibited lipid peroxidation strong correlation between induction both processes parallel antioxidants are suggestive causative role for hepatotoxicity.