title: New insights into antioxidant strategies against paraquat toxicity.
abstract: Paraquat (PQ, 1,1'-dimethyl-4-4'-bipyridinium dichloride) is a highly toxic quaternary ammonium herbicide widely used in agriculture, it exerts its toxic effects mainly because of its redox cycle through the production of superoxide anions in organisms, leading to an imbalance in the redox state of the cell causing oxidative damage and finally cell death. The contribution of mitochondrial dysfunction including increased production of reactive oxygen species besides the reduction in oxygen consumption as well as in the activity of some respiratory complexes has emerged as a key component in the mechanisms through which PQ induces cell death. Although several aspects of PQ-mitochondria interaction remain to be clarified, recent advances have been conducted with reproducible results. Currently, there is no treatment for PQ poisoning; however, several studies taking into account oxidative stress as the main mechanism of PQ-induced toxicity suggest an antioxidant therapy as a viable alternative. In fact, it has been shown that the antioxidants naringin, sylimarin, edaravone, Bathysa cuspidata extracts, alpha-lipoic acid, pirfenidone, lysine acetylsalicylate, selenium, quercetin, C-phycocyanin, bacosides, and vitamin C may be useful in the treatment against PQ toxicity. The main mechanisms involved in the protective effect of these antioxidants include the reduction of oxidative stress and inflammation and the induction of antioxidant defenses. Interestingly, recent findings suggest that the induction of nuclear factor erythroid like-2 (Nrf2), a major regulator of the antioxidant response, by some of the above-mentioned antioxidants, has been involved in the protective effect against PQ-induced toxicity.
authors.affiliation: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM) , University City, D.F. , Mexico.
authors.forename: T
authors.initials: T
authors.lastname: Blanco-Ayala
authors.forename: A C
authors.initials: AC
authors.lastname: Andérica-Romero
authors.forename: J
authors.initials: J
authors.lastname: Pedraza-Chaverri
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D004579:Electron Transport / Q000187:drug effects; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008928:Mitochondria / Q000473:pathology; D028361:Mitochondrial Diseases / Q000139:chemically induced; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000139:chemically induced; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D006540:Herbicides; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D010269:Paraquat