Efficacy of zinc treatment against iron-induced toxicity in rat hepatoma cell line H4-II-E-C3

Objective: In this study, we have attempted to explore the possible protection afforded by Zn with regard to its antioxidant potential properties in the iron-induced toxicity. Methods: Rat hepatoma cell line H4-II-E-C3 was treated with 150 mu M ZnSO4, 200 mu M FeSO4 or 150 mu M ZnSO4+ 200 mu M FeSO4 for 24 h. We studied the effect of metallothionein (MT), glutathione and metal (Fe and Zn) accumulation. We evaluated the levels of both MT-1 and MT-2 mRNAs, activities of antioxidant enzymes, and also determined the distribution of MT and cell death index. Results: The cotreatment produced highest levels of MT. Fe concentration was significantly lower in the Zn-Fe-treated cells compared with Fe-treated cells. In both Zn treatments, the superoxide dismutase/glutathione peroxidase ratio was similar to control. The cell death index was lower in the Zn-Fe-treated cells compared with Fe-treated cells. Conclusions: Zn may act as antioxidant by competitive inhibition of iron uptake by the divalent metal transporter and/or by MT induction.