Protective effects of apigenin against edifenphos-induced genotoxicity and cytotoxicity in rat hepatocytes

Edifenphos (EDF) is an organophosphorus pesticide with antifungal and anti-insecticidal properties. However, EDF accumulates in various agricultural products and causes potential hazards to human health. Although numerous reports have indicated EDF accumulation in agricultural products, toxic effects on cellular system is poorly understood. In the present study, we investigated the cytotoxicity and genotoxicity of EDF in rat hepatocytes and its amelioration by apigenin (a dietary flavonoid). Results showed that EDF inhibited the cell viability, induced oxidative stress, DNA damage, loss of mitochondrial membrane potential (DWm) and caspase-9/-3 activation in rat hepatocytes. Incubation of hepatocytes with N-acetyl cysteine (ROS scavenger) significantly abrogated the ROS generation and apoptosis caused by EDF. In addition, this study also showed that apigenin significantly suppressed the toxic effects of EDF by quenching ROS production thereby abrogating the caspase-9/-3 and apoptosis activation in hepatocytes. Taken together, the findings of this study demonstrate that EDF induces cytotoxicity and DNA damage in hepatocytes, and apigenin can be considered as an effective dietary anti-oxidant regimen against EDF- induced toxicity in cellular system. [GRAPHICAL ABSTRACT]