title: Mangiferin attenuates methylmercury induced cytotoxicity against IMR-32, human neuroblastoma cells by the inhibition of oxidative stress and free radical scavenging potential.
abstract: Mangiferin (MGN), a C-glucosylxanthone was investigated for its ability to protect against methylmercury (MeHg) induced neurotoxicity by employing IMR-32 (human neuroblastoma) cell line. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and clonogenic cell survival assays confirmed the efficacy of MGN supplementation in attenuating MeHg-induced cytotoxicity. Pre-treatment with MGN significantly (p<0.01) inhibited MeHg-induced DNA damage (micronuclei, olive tail moment and % tail DNA) thereby demonstrating MGN's antigenotoxic potential. Also, pre-treatment with MGN significantly reduced MeHg-induced oxidative stress, intra-cellular Ca(2+) influx and inhibited depolarization of mitochondrial membrane. MGN pre-treated cells demonstrated a significant (p<0.05) increase in the GSH and GST levels followed by a significant (p<0.05) decrease in malondialdehyde (MDA) formation. In addition, inhibition of MeHg induced apoptotic cell death by MGN was demonstrated by microscopic, Annexin-V FITC and DNA fragmentation assays and further confirmed by western blot analysis. The present findings indicated the protective effect of MGN against MeHg induced toxicity, which may be attributed to its anti-genotoxic, anti-apoptotic and anti-lipid peroxidative potential plausibly because of its free radical scavenging ability, which reduced the oxidative stress and in turn facilitated the down-regulation of mitochondrial apoptotic signalling pathways.
authors.affiliation: Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Karnataka, India.
authors.forename: Shubhankar
authors.initials: S
authors.lastname: Das
authors.forename: B
authors.initials: B
authors.lastname: Nageshwar Rao
authors.forename: B S
authors.initials: BS
authors.lastname: Satish Rao
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D045304:Cytochromes c / Q000378:metabolism; D048749:Cytokinesis / Q000187:drug effects; D019610:Cytoprotection / Q000502:physiology*; D004249:DNA Damage / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D042541:Intracellular Space / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008668:Metallothionein / Q000378:metabolism; D008767:Methylmercury Compounds / Q000494:pharmacology* / Q000633:toxicity*; D015162:Micronucleus Tests; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D009447:Neuroblastoma / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology; D014410:Tumor Stem Cell Assay; D044004:Xanthones / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D017304:Annexin A5; D000975:Antioxidants; C494826:BAX protein, human; D016166:Free Radical Scavengers; D008767:Methylmercury Compounds; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D014404:Tubulin; D050257:Tubulin Modulators; D044004:Xanthones; D051028:bcl-2-Associated X Protein; C525355:metallothionein-1, mouse; C013592:mangiferin; D045304:Cytochromes c; D008668:Metallothionein; C505409:Casp3 protein, mouse; D053148:Caspase 3; C004925:methylmercuric chloride; D002118:Calcium