title: Harmonization of Mangiferin on methylmercury engendered mitochondrial dysfunction.
abstract: Mangiferin (MGN), a C-glucosylxanthone abundantly found in mango plants, was studied for its potential to ameliorate methylmercury (MeHg) induced mitochondrial damage in HepG2 (human hepatocarcinoma) cell line. Cell viability experiments performed using 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide (MTT) showed protective property of MGN in annulling MeHg-induced cytotoxicity. Conditioning the cells with optimal dose of MGN (50 µM) lowered MeHg-induced oxidative stress, calcium influx/efflux, depletion of mitochondrial trans-membrane potential and prevented mitochondrial fission as observed by decrease in Mitotracker red fluorescence, expression of pDRP1 (serine 616), and DRP1 levels. MGN pre-treated cells demonstrated elevation in the activities of glutathione (GSH), Glutathione-S-transferase (GST), Glutathione peroxidase (GPx), Glutathione reductase (GR), reduced levels of Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) and mitochondrial electron transport chain (ETC) enzyme complexes. In addition, the anti-apoptotic effect of MGN was clearly indicated by the reduction in MeHg-induced apoptotic cells analyzed by flowcytometric analysis after Annexin V-FITC/propidium iodide staining. In conclusion, the present work demonstrates the ability of a dietary polyphenol, MGN to ameliorate MeHg-mediated mitochondrial dysfunction in human hepatic cells in vitro. This hepatoprotective potential may be attributed predominantly to the free radical scavenging/antioxidant property of MGN, by facilitating the balancing of cellular Ca2+ions, maintenance of redox homeostasis and intracellular antioxidant activities, ultimately preserving the mitochondrial function and cell viability after MeHg intoxication. As MeHg intoxication occurs over a period of time, continuous consumption of such dietary compounds may prove to be very useful in promoting human health. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 630-644, 2017.
authors.affiliation: Department of Radiation Biology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka, India, 576104.
authors.forename: Shubhankar
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of Biotechnology, School of Life Sciences, Manipal University, Manipal, Karnataka, India, 576104.
authors.forename: Ajanta
authors.initials: A
authors.lastname: Paul
authors.affiliation: Department of Radiation Biology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka, India, 576104.
authors.forename: Kamalesh D
authors.initials: KD
authors.lastname: Mumbrekar
authors.affiliation: Department of Radiation Biology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka, India, 576104.
authors.forename: Satish B S
authors.initials: SB
authors.lastname: Rao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008767:Methylmercury Compounds / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D008767:Methylmercury Compounds; D017382:Reactive Oxygen Species; D044004:Xanthones; C013592:mangiferin; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione
keywords: heavy metal toxicity; mitochondria; oxidative stress; polyphenols