QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Peterson, F. J. Articles by Holtzman, J. L. Search for Related Content PubMed PubMed Citation Articles by Peterson, F. J. Articles by Holtzman, J. L.

Potentiation of Acute Acetaminophen Lethality by Selenium and Vitamin E Deficiency in Mice

Research Service, Veterans Administration Medical Center, Minneapolis, MN 55417 and Departments of Pharmacology and Medicine, University of Minnesota, Minneapolis, MN 55455

The effects of selenium, vitamin E, and DL-methionine deficiency on the acute lethality and hepatotoxicity of acetaminophen in male CD-1 mice were studied. Vitamin E and selenium deficiencies led to an increase in the acute lethality of acetaminophen, with a decrease in the LD₅₀ from 376 to 84 mg/kg. These dietary deficiencies impaired the inducibility of the hepatic microsomal mixed function oxidase system by phenobarbital, but on the basis of the covalent binding of acetaminophen to microsomes, these treatments did not alter the activation of acetaminophen to a reactive intermediate by this system. Addition of methionine to the deficient diet restored hepatic glutathione content to control levels but did little to protect against the acute lethality of acetaminophen. In methionine-supplemented animals, the addition of either selenium or vitamin E increased the LD₅₀ of acetaminophen to 167 and 200 mg/kg, respectively. Administration of a sublethal, toxic dose of acetaminophen (LD₃₀) to the methionine-supplemented and selenlum- and vitamin E-deficient mice did not produce any hepatic damage as evidenced by a lack of plasma aminotransferase elevation. In view of the known antioxidant effects of vitamin E and selenium, these data suggest the involvement of a reactive radical in the acute lethality of acetaminophen and further suggest that death from acute acetaminophen overdose in chronic selenium- and vitamin E-deficient mice may be unrelated to liver necrosis.

KEY WORDS: • mice • acetaminophen • selenium • vitamin E • methionine

¹ To whom correspondence should be addressed at Sandoz Nutrition, 5320 West 23rd Street, Minneapolis, MN 55440.

Manuscript received 9 May 1990. Revision accepted 9 July 1991.

This article has been cited by other articles:

				S. Yalcin, A Bilgili, I Onbasilar, G Eraslan, and M Ozdemir Synergistic action of sodium selenite and N-acetylcysteine in acetaminophen-induced liver damage Human and Experimental Toxicology, May 1, 2008; 27(5): 425 - 429. [Abstract] [PDF]