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Vitamin E Is Protective against Iron Toxicity and Iron-Induced Hepatic Vitamin E Depletion in Mice^{1, 2, 3,}

Department of Veterinary Physiological Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada, S7N 0W0

This study examined the effect of excess dietary iron on liver function, iron and vitamin E status and the protective activity of vitamin E. Consumption of excess dietary iron (3000, 5000, 8000 mg iron/kg/diet) compared with consumption of the control diet (120 mg iron/kg diet) by weanling male CD-1 mice for 7 wk resulted in accumulation of iron in liver, increased relative liver weights and a reduction in hepatic vitamin E stores. The concentration of vitamin E in the liver was negatively correlated with dietary iron concentration (r = 0.998). Weekly administration of vitamin E (20 mg/kg, subcutaneously) prevented iron-induced liver damage without altering hepatic iron stores. Pretreatment of adult male CD-1 mice with a single subcutaneous dose of vitamin E (20 mg/kg body wt) 24 h prior to a lethal dose of iron (60 mg/kg, intraperitoneally) resulted in 100% protection. A similar dose of vitamin E given 5, 30 or 60 min (intravenously) after iron intoxication enhanced survival to 90, 70 and 80%, respectively, compared with the untreated control group. Vitamin E treatment 30 min after iron intoxication reduced mortality by 75% compared with intravenous treatment with 10 mg/kg of deferoxamine (Desferal). Data in this study indicate that vitamin E may be a useful antidote for iron toxicoses and that iron-induced depletion of vitamin E may play a role in the pathogenesis of iron toxicity.

KEY WORDS: • vitamin E • iron toxicity • mice • deferoxamine • liver damage

¹ Presented in part in poster form at Society of Toxicology of Canada, 25th Annual Symposium, December 1992, Montreal, Quebec, Canada [Omara, F. O. & Blakley, B. R. (1992) The effect of -tocopherol on iron toxicity in mice. Soc. Tox. Canada 25th Annu. Sympos. (Student Poster Session(].

² Funded by the Natural Sciences and Engineering Research Council of Canada.

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom correspondence should be addressed.

Manuscript received 8 March 1993. Revision accepted 26 May 1993.