title: Curcumin attenuates arsenic-induced hepatic injuries and oxidative stress in experimental mice through activation of Nrf2 pathway, promotion of arsenic methylation and urinary excretion.
abstract: Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Curcumin is a natural phenolic compound with impressive antioxidant properties. What's more, curcumin is recently proved to exert its chemopreventive effects partly through the activation of nuclear factor (erythroid-2 related) factor 2 (Nrf2) and its antioxidant and phase II detoxifying enzymes. In vivo, we investigated the protective effects of curcumin against arsenic-induced hepatotoxicity and oxidative injuries. Our results showed that arsenic-induced elevation of serum alanine amino transferase (ALT) and aspartate aminotransferase (AST) activities, augmentation of hepatic malonaldehyde (MDA), as well as the reduction of blood and hepatic glutathione (GSH) levels, were all consistently relieved by curcumin. We also observed the involvement of curcumin in promoting arsenic methylation and urinary elimination in vivo. Furthermore, both the hepatic Nrf2 protein and two typically recognized Nrf2 downstream genes, NADP(H) quinine oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), were consistently up-regulated in curcumin-treated mice. Our study confirmed the antagonistic roles of curcumin to counteract inorganic arsenic-induced hepatic toxicity in vivo, and suggested that the potent Nrf2 activation capability might be valuable for the protective effects of curcumin against arsenic intoxication. This provides a potential useful chemopreventive dietary component for human populations.
authors.affiliation: Department of Health Laboratory Technology, School of Public Health, China Medical University, 110001 Shenyang, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Gao
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Duan
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Dandan
authors.initials: D
authors.lastname: Dong
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Guifan
authors.initials: G
authors.lastname: Sun
authors.forename: Bing
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001151:Arsenic / Q000493:pharmacokinetics / Q000633:toxicity / Q000652:urine; D020261:Arsenic Poisoning / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control* / Q000652:urine; D003474:Curcumin / Q000627:therapeutic use*; D019587:Dietary Supplements; D005260:Female; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D048550:Hepatic Insufficiency / Q000209:etiology / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D008565:Membrane Proteins / Q000819:agonists / Q000378:metabolism; D050217:Metabolic Detoxication, Phase II; D008745:Methylation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000819:agonists* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D005978:Glutathione; D003474:Curcumin; D001151:Arsenic
keywords: ALT; ARE; AST; Arsenic; Curcumin; DMA; GSH; GSH-Px; HO-1; Liver; MDA; MMA; Methylat; NADP(H) quinine oxidoreductase 1; NQO1; Nrf2; Oxidative stress; PMR; SMR; T-As; alanine amino transferase; antioxidant response element; aspartate aminotransferase; dimethylarsinic acid; glutathione; glutathione peroxidase; heme oxygenase-1; iAs; inorganic arsenic; malonaldehyde; monomethylarsonic acid; nuclear transcription factor NF-E2-related factor 2; primary methylation ratio; secondary methylation ratio; total arsenic