Abstract:
Objective To observe the effects of arsenic on the expressions of c-fos,c-jun and cell apoptosis in rat hippocampus,and to explore the neurotoxic mechanism of arsenic.
Methods Fifty-six Sprague-Dawley(SD)rats were randomly divided into 4 groups:low-,medium-,and high-dose group(sodium arsenite:5,10 and 20 mg/kg)and the control group.The exposuse groups were exposed to sodium arsenite by intragastric admintration and the control group was treated with distilled water for 15 days,and then all the rats were sacrificed.The positive ratio of c-fos and c-jun expressions and index of cell apoptosis in rat hippocampus were determined with immunohistochemical and terminal deoxynuel eotidyl transferase-mediated dUTP nick end-labeling(TUNEL)method.
Results The positive ratios of c-fos and c-jun expression in rat hippocampus of low-,medium- and high-dose groups were 54.86±10.35%,64.18±6.23%,and 73.69±5.52% and 0.434±0.044%,0.620±0.067%,and 0.711 ±0.026%,and the index of apoptosis was 37.80±5.28%,48.49±5.25%,and 72.30±4.81%,respectively,with significant differences compared with those of the control group (
P<0.01 for all) and clear dose-response relationships.The correlation analysis demonstrated that the positive ratio of c-fos and c-jun expression in rat hippocampus in the three arsenic exposure groups correlated positively with the index of apoptosis,and the positive expression rate of c-fos was also positively correlated with that of c-jun.
Conclusion The results demonstrate that arsenic promotes the expressions of c-fos and c-jun in rat hippocampus and leads to apoptosis of neuron.The overexpression of c-fos and c-jun in brain may be one of the reasons that results in neurotoxicity of arsenic.