Immunomodulatory role of piperine in deltamethrin induced thymic apoptosis and altered immune functions

Deltamethrin (DLM), a well-known pyrethroid insecticide, is a potent immunotoxicant. In rodents, it is primarily characterized by marked thymic apoptosis. Mechanism of DLM induced thymic apoptosis in primary murine thymocytes has been recently explored. Oxidative stress and activation of caspase dependent pathways appear to be involved in the DLM induced thymic injury. Thus, for the amelioration of its effect, this study has been designed to first observe the binding affinity of piperine to immune cell receptors and its protective effects on the DLM induced immunotoxicity under in vitro condition. The docking results demonstrated that piperine has good binding affinity towards CD4 and CD8 receptors. In vitro study results have shown that piperine (1, 10 and 50 μg/ml) increased cell viability in a concentration dependent manner. The early activated markers of apoptosis such as enhanced reactive oxygen species (ROS) and caspase-3 activation by DLM was significantly reduced by piperine treatment. GSH depletion induced by DLM has been also restored by piperine treatment. At 18 h, all concentration of piperine (1, 10 and 50 μg/ml) significantly ameliorated the DLM induced apoptosis. Further, DLM induced phenotypic changes were mitigated by the piperine. In addition, piperine also restored the cytokine levels, which were suppressed by DLM treatment. These findings strongly indicate the anti-oxidative, anti-apoptotic and chemo-protective ability of piperine in the DLM induced thymic apoptosis.