Effects of Fe, salicylate and Zn on metallothionein and lipid peroxidation in vivo

Abstract

Control rats and rats pretreated with two i.p. injections of 15 mg/kg Fe, given as FeCl3, received either one oral dose of 700 mg/kg salicylic acid, given as Na salicylate, or 100 mumol ZnCl2/kg s.c., or salicylate and ZnCl2. In the rats given Fe this treatment was simultaneous with the second iron injection. Salicylate and Fe alone caused a small increase in lipid peroxidation (LPO) measured as malondialdehyde formation in the liver by means of the thiobarbiturate method. When given together, however, Fe and salicylate caused a drastic increase of LPO in liver, which was reduced by the simultaneous injection of ZnCl2. Hepatotoxicity as determined histochemically by lipid storage paralleled LPO. The protective effect of Zn on LPO and hepatotoxicity was not correlated to metallothionein induction in liver. The protective effect of Zn can be explained by the competition of Fe with Zn for binding to salicylate which reduces Fe-salicylate-induced LPO and hepatotoxicity.