Fig. 13. Putative mechanism of acephate toxicity (ROS-mediated) in Drosophila melanogaster. Lipophilic acephate can easily penetrate the plasma membrane to enter the cell. CYP450 on the endoplasmic reticulum (ER) oxidizes acephate into a phase-I metabolite which transforms into a phase-II metabolite in the cytosol by GST activity. Oxidation of acephate in the ER liberates excessive superoxide anion (O₂˙^–) which can be converted into H₂O₂ by SOD. H₂O₂ may undergo two fates: one includes its breakdown to H₂O while another comprises its conversion into a more reactive hydroxyl (˙OH) radical. ROS in the form of O₂˙^– and ˙OH can overwhelm the intrinsic antioxidant system of the body and can induce oxidative stress. ROS can damage proteins, DNA and lipid moieties of the cell membrane. Additionally, ROS may trigger the Dmp53-rpr mediated apoptotic cascade (see the text for details) at the sub-cellular level. Increased cell death results in tissue/organ damage that reduces the physical activities and life span of the organism.