Fig. 11
Proposed mechanisms of accidental co-exposure of experimental rats’ models to Lead and Furan in diet and water, respectively. Furan is converted to cis-but-ene-1,4-dialdehyde. This intermediate induces oxidative stress and inflammation by activating xanthine oxidase and myeloperoxidase to generate abundant ROS, including O2−, H2O2, and HOCl. On the other hand, Pb triggers the Fenton and Haber–Weiss reaction to generate abundant OH−. These intermediates activate iNOS which mediate the generation of NO and other pro-inflammatory cytokines such as IL-1β. Unresolved oxidative stress and inflammation will trigger oxidative DNA damage and increase the tissue level of 8-OHdG. Increases in the 8-OHdG DNA adduct will trigger the activation of p53, instructing PUMA to activate Bax while repressing the activity of Bcl-2. Bax enters the mitochondria of the hepatocytes and nephrons and causes the evolution of cytochrome C, which binds to apaf to form apoptosome with concurrent activation of caspase-9. Active caspase-9 then activates caspase-3 – the executioner of programmed cell death