A Calcium Channel Blocker Nicardipine Protects Neurons From Zinc-Induced Toxicity in Rat Hippocampus

Abstract

The neurotoxicity is an important problem in medicine. The present study was designed to investigate the changes in pyramidal cell density of rat hippocampus after intracortical zinc sulphate (ZnSO<inf>4</inf>) and calcium channel blocker nicardipine administration. Animals were divided into three groups as control, zinc and zinc+nicardipine groups. Zinc sulphate (500 μg/kg) was injected intracortically into 2 mm lateral of Bregma. The same volume of saline (2μl) was given to the rats belonging to control group. Rats in the third group, zinc + nicardipine were injected in to same injection point. Animal groups were observed for one week. The zinc + nicardipine group received daily nicardipine (10mg/kg/day) for seven days. After a week, the rats were perfused intracardially with neutral formaline. The hippocampal sections were stained with hematoxylen-eosine. Pyramidal cells per unit length (mm) were counted under light microscope (with 400x magnification). The density of pyramidal cell was found as follows (values presented for each group are belong to right CA1, right CA2, right CA3, left CA1, left CA2, left CA3 respectively): control groups; 126.2 ± 4.5 neuron/mm, 117.3 ± 6.2 neuron/mm, 113.6 ±4.0 neuron/mm, 129.9 ± 4.0 neuron/mm, 129.8 ± 5.0, 127.7 ± 3.3, zinc groups; 38.3 ± 1.3 neuron/mm, 36.5 ± 1.6 neuron/mm, 34.1 ± 1.2, 35.0 ± 1.4 neuron/mm, 33.9 ± 1.5 neuron/mm, 32.9 ± 1.2 neuron/mm, zinc + nic groups; 87.9 ± 1.4 neuron/mm, 89.9 ± 3.7 neuron/mm, 82.2 ± 2.8 neuron/mm, 91.2 ± 3.8 neuron/mm, 91.9 ± 4.6 neuron/mm, 84.3 ± 4.0 neuron/mm. The differences between groups were found to be statistically significant (p<0.001). These results suggest that nicardipine considerably reverses the decrease in pyramidal cell density probably caused by zinc administration into the hippocampus of rat. This effect may be due to the prevention of excessive calcium influx and hence the prevention of cell loss. The results also suggest a possible therapeutic role for calcium channel blocker nicardipine in neurodegenerative diseases.