The ââ?¬Å?Mitochondrial Free Radical Theory of Agingââ?¬Â (MFRTA) hypothesizes that\nreactive oxygen species (ROS) arising from aged and/or defective mitochondria\nare associated with the pathogenesis of various age-related diseases. The\nglutathione antioxidant response, in particular glutathione redox cycling, is a\ncritical mechanism for protection against ROS-induced cell death. Over the past\nfew decades, a number of phytochemicals [such as curcumin, epigallocatechin\ngallate (EGCG), resveratrol and schisandrin B (Sch B)], which all possess the ability\nto elicit a nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated antioxidant\nresponse, have been identified. Despite the fact that these phytochemicals can\nproduce cyto/tissue protection against oxidant-induced injury in various types of\ncultured cells/rodent tissues, the underlying protective mechanism can vary. While\ncurcumin, EGCG and resveratrol likely confer cytoprotection via the activation of\nglutathione S-transferase and glutathione peroxidase, Sch B is thought to produce\nits protective effect via the induction of glutathione redox cycling, which is of\nprimary importance in preventing cell death. Recent studies have suggested\nthat the electrophilicity of phytochemicals and/or their metabolites determines\ntheir ability to activate Nrf2 by the oxidative modification of a cysteine residue\non the repressor of Nrf2 [namely, Kelch-Like ECH-Associated Protein 1 (Keap1)].\nThe differences in structures of phytochemicals could produce differential\naccessibility to this critical cysteine residue of Nrf2/Keap1, presumably leading to\nvarying degrees of Nrf2 activation and antioxidant gene expression. In the hope of\ndeveloping safe and effective interventions for protection against oxidant-induced\ninjuries, further studies are required to define the protective mechanism(s),\nparticularly the array of antioxidant enzyme expressions, induced by the various\nphytochemicals.
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