Effect of antioxidants on vanadate-induced toxicity towards isolated perfused rat livers.
The effect of trolox C, a water soluble vitamin E analogue, propyl gallate and ascorbate on vanadate hepatotoxicity was investigated in vitro. In isolated perfused livers from fasted rats, sodium orthovanadate (2 mmol/l) led to toxic responses including reduction of oxygen consumption, release of cytosolic (glutamate-pyruvate-transaminase (GPT) and lactate dehydrogenase (LDH)) and mitochondrial (glutamate-dehydrogenase (GLDH)) enzymes, intracellular accumulation of calcium, a marked depletion of glutathione (GSH) and an enhanced formation and release of thiobarbituric acid- (TBA) reactive material. Trolox C and propyl gallate inhibited the release of GPT and LDH partially and that of GLDH totally, but had no influence on vanadate-induced calcium accumulation or on the reduction of oxygen consumption. Both agents suppressed vanadate-induced lipid peroxidation (LPO) and partially prevented GSH depletion. Ascorbate failed to provide any protection probably due to the interference of its pro-oxidant potential with its antioxidant activity. The protection, mainly of mitochondria, afforded by those agents which also inhibited LPO substantiates our previous findings that the pro-oxidant activity of vanadate is mainly responsible for its direct hepatotoxic actions [2]. Besides, reduction of organ perfusion rate due to vasoconstriction also contributes to vanadate toxicity, but oxidative stress is not involved in this indirect toxic activity.
Younes
M
M
Institute of Toxicology, Medical University of Lübeck, Germany.
Kayser
E
E
Strubelt
O
O
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D011435:Propyl Gallate / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014638:Vanadates / Q000037:antagonists & inhibitors* / Q000633:toxicity
D000975:Antioxidants; D002839:Chromans; D014638:Vanadates; D011435:Propyl Gallate; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D002118:Calcium