Mitigating effects of apigenin on edifenphos-induced oxidative stress, DNA damage and apoptotic cell death in human peripheral blood lymphocytes

Abstract

Edifenphos (EDF) is an Organophosphorus pesticide and used in agriculture for pest control. However, EDF has been shown to accumulate in agricultural products and causes hazards to human health. Although reports are available regarding environmental impact of EDF, toxic effects of EDF on human cellular system especially immune cells have not been elucidated. In this study, genotoxicity and cytotoxicity of EDF on human peripheral blood lymphocytes and its amelioration by apigenin (dietary flavonoid) was investigated. We demonstrated that EDF inhibited cell viability, and induced oxidative stress and DNA damage in lymphocytes. In addition, results indicate that EDF induced apoptosis in lymphocytes concurrent with ROS generation, loss of mitochondrial membrane potential, up-regulation of Bax and caspase-9/-3 activation. Mechanistically, incubation of lymphocytes with N-acetylcysteine (ROS scavenger) abrogated the ROS generation and apoptosis caused by EDF. These findings suggest that ROS generation by EDF acts as an upstream signal leading to DNA damage and apoptosis in lymphocytes. This study also showed that apigenin could potentially attenuate EDF-induced oxidative stress, DNA damage and apoptosis in lymphocytes. Collectively, these results suggest that EDF exerts cytotoxicity and DNA damage in lymphocytes, and apigenin could be a potent dietary anti-oxidant regimen against EDF-induced toxicity on human health.