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To investigate the underlying mechanism of neurotoxicity of cadmium, we examined the effects of intraperitoneal injection of cadmium on messenger RNA (mRNA) expression of Bcl-2 (B-cell lymphoma 2) and Bax (Bcl2-associated x) genes and caspase-3/7 activation in rat hippocampus and frontal cortex. Twenty-eight male Wistar rats weighing 200-250 g were randomly divided into four groups. Control group received saline and three other groups received cadmium at doses of 1, 2 and 4 mg/kg (body weight) for 15 successive days. One day after the last injection, the hippocampus and frontal cortex were dissected and removed and then the expression of Bcl-2 and Bax genes was evaluated using real-time polymerase chain reaction and apoptotic studies was done using caspase-3/7 activation assay. Cadmium reduced the mRNA level of Bcl-2 in the control group at doses of 1 ( p < 0.01), 2 and 4 mg/kg ( p < 0.001) in rat hippocampus and cortex cells. The mRNA level of Bax increased significantly compared to the control group at the doses of 1 ( p < 0.05), 2 and 4 mg/kg ( p < 0.001) in rat hippocampus. The mRNA level of Bax was increased significantly compared to the control group at the doses of 2 and 4 mg/kg ( p < 0.001) in rat cortex cells. Cadmium increased caspase-3/7 activity at doses of 1, 2 and 4 mg/kg in rat hippocampus. Caspase-3/7 activity was increased significantly at dose of 4 mg/kg in rat cortex. This decreased Bcl-2/Bax mRNA ratio induces cell apoptosis. Apoptotic effect of cadmium may be through the mitochondrial pathway by the activation of caspase-3/7.

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Although not fully recognized, the neurotoxic effects of silver nanoparticles (Ag-NPs) are thought to occur through induction of oxidative stress and apoptosis. To investigate the exact underlying molecular mechanism, we aimed to explore the apoptotic effects of intraperitoneal injection of Ag-NPs and investigated the possible attributed changes in the mRNA expression of Bcl-2 and Bax genes in the rat hippocampus. Two in vivo sets of experiments, one to demonstrate apoptosis and the other to assess gene expression, were conducted on male Wistar rats. In each set, the first group, acting as control, received saline and the other three groups received Ag-NP at doses of 100, 200, and 400 ppm for five successive days. Ten days after the last injection, hippocampal tissue of the first set of rats was assessed for apoptosis using terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate nick-end labeling staining. In the second set of experiments, mRNA expression of Bcl-2 and Bax genes was evaluated using real-time polymerase chain reaction. Ag-NP treatment was shown to induce apoptosis in a dose-dependent manner. Furthermore, Ag-NP reduced mRNA level of Bcl-2 in the rat hippocampal cells at all investigated doses compared to the control group ( p < 0.001). The mRNA level of Bax, on the other hand, was increased in these cells. The increase was significant compared to the control group at the doses of 200 ppm ( p < 0.05) and 400 ppm ( p < 0.001). Our results show that Ag-NPs reduce Bcl-2 and increase Bax genes expression, resulting in increased Bax/Bcl-2 ratios in rat hippocampal cells. This altered gene expression induces cell apoptosis and contributes to the neurotoxicity of Ag-NPs.

No abstract