Inhibition of amine-nitrite hepatotoxicity by alpha-tocopherol
Kamm, J.J.; Dashman, T.; Newmark, H.; Mergens, W.J.
Toxicology and Applied Pharmacology 41(3): 575-583
1977
ISSN/ISBN: 0041-008X PMID: 918988 Document Number: 123935
Studies in vitro have shown that .alpha.- and .gamma.-tocopherol, but not .alpha.-tocopherolquinone, react with sodium nitrite with the resulting disappearance of nitrite anion from the reaction mixture. The rate of this reaction is accelerated as the pH of the mixture is made more acidic. The destruction of nitrite by .alpha.-tocopherol in simulated gastric fluid suggested that .alpha.-tocopherol might prevent the formation of nitrosamines which are formed by the interaction of nitrosatable amines and nitrite in the acid environment of the mammalian stomach. In rats orally treated with aminopyrine plus sodium nitrite, .alpha.-tocopherol can completely block the elevation in SGPT which is induced by feeding aminopyrine plus sodium nitrite alone. Evidence is presented which suggests that .alpha.-tocopherol affords protection in this animal model for amine-nitrite toxicity by preventing the nitrosative cleavage of aminopyrine to dimethylnitrosamine by sodium nitrite, in the acidic environment of the rat's stomach.