4-Nitrophenol induces activation of Nrf2 antioxidant pathway and apoptosis of the germ cells in rat testes.

The potential of 4-nitrophenol (PNP) to affect testicular function of rats was assessed by intratesticular injection (IT). The protective effects of phytosterin (PS) on PNP-induced injury were assessed. Rats were sacrificed on days 1, 3, and 7 after IT of PNP (0.1 M, 50 μl). PNP induced hemorrhage in intertubular areas and denudation of germinal epithelium. The expression of caspase-3 and sperm abnormalities were significantly increased (P < 0.05). The concentrations of testosterone in serum were significantly increased (P < 0.05) on the 1st and 3rd day. PNP induced oxidative stress in testes, which manifested increased SOD, CAT, GSH-Px activities, and increases in MDA, GSH, H2O2 concentrations (P < 0.05). The Nrf2 antioxidant pathway was activated as indicated by increased expression of Nrf2, HO-1, and GCLC mRNA (P < 0.05). Moreover, supplementation with PS resulted in an amelioration of PNP-induced oxidative damage. These results suggest that PNP induced activation of Nrf2 antioxidant pathway and apoptosis of the germ cells.