Objective To investigate the effects of carbon disulfide (CS2) on testicular apoptosis via mitochondrial pathways, explore its possible molecular mechanisms, and observe the intervention of cyclosporin A (CsA) on cell apoptosis.
Methods Forty-eight SD male rats were randomly divided into six groups. Three groups were exposed to CS2 at designed concentrations (50, 250, 1 250 mg/m3) by inhalation 2 h/d and 5 d/week for 10 weeks. Fresh air was inhaled only by rats of the control group. The other two groups were treated with CS2 (1250mg/m3) plus CsA (12.5mg/kg) and CsA (12.5mg/kg) alone respectively. CsA was prepared before gavage to the designed solutions by milk as solvent according to rat body weights. The histopathological changes in rats' testes were observed after HE staining and apoptosis by TUNEL. Western Blot was applied to detect the expression of Cyt C, Procaspase-9, Procaspase-3, Bcl-xL, and Bad protein in each group.
Results The histopathological injuries of rats' testes stained by HE were aggravated with the increasing of CS2 concentration. The apoptosis indices of the middle and high concentration groups were higher than that of the control group (P < 0.05). After treated with CsA, the histopathological injuries of rats' testes were alleviated, and also the apoptosis index was declined significantly compared with the high concentration group (P < 0.05) but higher than that of the CsA only group (P < 0.05). Compared with the control group, the expressions of Cyt C and Bad protein were increased, whereas the expressions of Procaspase-9, Procaspase-3, and Bcl-xL were lowered in different concentration groups (P < 0.05). In the CS2 plus CsA group, the expression of Cyt C was decreased and the expression of Bcl-xL was increased compared with the high concentration group (both P < 0.05). Varied changes were observed in the expressions of Procaspase-9 and Bad protein in the CS2 plus CsA group; however, there was no statistical difference in comparison with the high concentration group.
Conclusion CS2 could induce testicular apoptosis through mitochondrial pathways. Meanwhile, CsA might regulate the expression of proteins related to mitochondrial pathways.
DownLoad: