Deltamethrin-induced testicular apoptosis in rats: the protective effect of nitric oxide synthase inhibitor

This study is the first to examine and characterize the testicular apoptosi s which might be induced due to exposure of male rats to deltamethrin. Furt hermore, the role which might be played by nitric oxide (NO), as well as th e other reactive oxygen species (ROS) in controlling this testicular apopto sis was assessed. Apoptosis was evaluated by DNA fragmentation detected by agarose gel electrophoresis and cellular morphology on testicular tissue se ctions. It was found that administration of deltamethrin (1 mg/kg daily for 21 days) to animals resulted in characteristic DNA migration patterns (lad dering), thereby providing evidence that apoptosis is the major mechanism o f cell death in the testicular tissues. In addition, histopathological exam ination of testicular tissue sections showed that apoptosis was confined to the basal germ cells, primary and secondary spermatocytes. These changes, in addition to the appearance of Sertoli cell vacuoles in deltamethrin-into xicated animals, indicates the suppression of spermatogenesis. At the same time, the plasma levels of both NO and lipid peroxides measured as malondia ldehyde (MDA) were found to be significantly increased in deltamethrin-trea ted animals. Administration of NO synthase (NOS) inhibitors such as NG-nitr o monomethyl L-arginine hydrochloride (L-NMMA, 1 mg/kg) to rats 2 h before exposure to deltamethrin was effective in the reduction of the typically te sticular apoptotic DNA fragmentation pattern and the associated histopathol ogical changes. These findings may suggest that deltamethrin-induced testic ular apoptosis is mediated by NO. Therefore, the pharmacological manipulati on of apoptosis by selective NOS inhibitors such as L-NMMA may offer new po ssibilities for the control of deltamethrin-induced testicular dysfunction and infertility in the future. (C) 1999 Elsevier Science Ireland Ltd. All r ights reserved.