title: Sulforaphane protects Microcystin-LR-induced toxicity through activation of the Nrf2-mediated defensive response.
abstract: Microcystins (MCs), a cyclic heptapeptide hepatotoxins, are mainly produced by the bloom-forming cyanobacerium Microcystis, which has become an environmental hazard worldwide. Long term consumption of MC-contaminated water may induce liver damage, liver cancer, and even human death. Therefore, in addition to removal of MCs in drinking water, novel strategies that prevent health damages are urgently needed. Sulforaphane (SFN), a natural-occurring isothiocyanate from cruciferous vegetables, has been reported to reduce and eliminate toxicities from xenobiotics and carcinogens. The purpose of the present study was to provide mechanistic insights into the SFN-induced antioxidative defense system against MC-LR-induced cytotoxicity. We performed cell viability assays, including MTS assay, colony formation assay and apoptotic cell sorting, to study MC-LR-induced cellular damage and the protective effects by SFN. The results showed that SFN protected MC-LR-induced damages at a nontoxic and physiological relevant dose in HepG2, BRL-3A and NIH 3T3 cells. The protection was Nrf2-mediated as evident by transactivation of Nrf2 and activation of its downstream genes, including NQO1 and HO-1, and elevated intracellular GSH level. Results of our studies indicate that pretreatment of cells with 10muM SFN for 12h significantly protected cells from MC-LR-induced damage. SFN-induced protective response was mediated through Nrf2 pathway.
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, CAS, People's Republic of China.
authors.forename: Nanqin
authors.initials: N
authors.lastname: Gan
authors.forename: Lixin
authors.initials: L
authors.lastname: Mi
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Sun
authors.forename: Guofei
authors.initials: G
authors.lastname: Dai
authors.forename: Fung-Lung
authors.initials: FL
authors.lastname: Chung
authors.forename: Lirong
authors.initials: L
authors.lastname: Song
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D017879:Isothiocyanates; D008387:Marine Toxins; D050217:Metabolic Detoxication, Phase II; D051379:Mice; D052998:Microcystins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D041681:NIH 3T3 Cells; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D018508:Water Purification / Q000379:methods
chemical_list: D000975:Antioxidants; D017879:Isothiocyanates; D008387:Marine Toxins; D052998:Microcystins; D051267:NF-E2-Related Factor 2; D020011:Protective Agents; D013454:Sulfoxides; D013861:Thiocyanates; C057862:cyanoginosin LR; C016766:sulforaphane; D005978:Glutathione