The Effect of Neuronal Nitric Oxide Synthase Inhibitor 7-Nitroindazole on the Cell Death Induced by Zinc Administration in the Brain of Rats

Abstract

Aim: To evaluate the effect of the neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI) on hippocampal cell loss induced by zinc hemisulfate salt (ZnSO4-7H2O) treatment. Materials and Methods: Rats were divided into 3 groups (n = 21; 7 rats in each group): Control, Zinc, and Zinc+7-NI. In the Zinc and Zinc+7-NI (pretreatment) groups, ZnSO4 7H2O was applied intracortically to the left sensory motor cortex. The 7-NI (50 mg/kg) was injected into the third group (Zinc+7-NI) intraperitoneally 20 min prior to zinc application and daily for the next 7 days. Cell loss in the left and right hippocampal hemispheres was quantified by optical fractionator, which is a relatively unbiased and reliable stereological counting method. Results: Zinc produced decreases of 43.5% and 46.1% in the number of viable neurons in the left and right hippocampal hemispheres, respectively, in comparison with control values. In the Zinc+7-NI group, cell losses were 16.2% and 18.5% in the left and right hemispheres, respectively, in the same conditions. Thus, 7-NI exerted a significant neuroprotective effect against zinc-induced cell loss in the rat hippocampus (P < 0.05). Conclusions: These results suggest that nitric oxide contributes to the hippocampal cell loss induced by zinc sulfate and that the prevention of nitric oxide formation by nNOS blockade can reduce this cell loss.