title: Attenuative role of mangiferin in oxidative stress-mediated liver dysfunction in arsenic-intoxicated murines.
abstract: Mangiferin (MAG), a natural xanthone mainly derived from mangoes, possesses great antioxidative potentials. The present study has been carried out to investigate the hepato-protective role of MAG, against arsenic (As)-induced oxidative damages in the murine liver. As, a well-known toxic metalloid, is ubiquitously found in nature and has been reported to affect nearly all the organs of the human body via oxidative impairment. Administration of As in the form of sodium arsenite (NaAsO2) at a dose of 10 mg/kg body weight for 3 months abruptly increased reactive oxygen species (ROS) level, led to oxidative stress and significantly depleted the first line of antioxidant defense system in the body. Moreover, As caused apoptosis in hepatocytes. Treatment with MAG at a dose of 40 mg/kg for body weight for 30 days simultaneously and separately after NaAsO2administration decreased the ROS production and attenuated the alterations in the activities of all antioxidant indices. MAG also protected liver against the NaAsO2-induced apoptosis and disintegrated hepatocytes, thus counteracting with As-induced toxicity. It could significantly inhibit the expression of different proapoptotic caspases and upregulate the expression of survival molecules such as Akt and Nrf2. On inhibiting Akt (by PI3K inhibitor, LY294002) and ERK1/2 (by ERK1/2 inhibitor, PD98059) specifically, caspase 3 got activated abolishing mangiferin's protective role on As-induced hepatotoxicity. So here, we have briefly elucidated the signaling cascades involved in As-induced apoptotic cell death in the liver and also the detailed cellular mechanism by which MAG provides protection to this organ. © 2016 BioFactors, 42(5):515-532, 2016.
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Sukanya
authors.initials: S
authors.lastname: Saha
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Kahkashan
authors.initials: K
authors.lastname: Rashid
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Pritam
authors.initials: P
authors.lastname: Sadhukhan
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Namrata
authors.initials: N
authors.lastname: Agarwal
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, India. parames@jcbose.ac.in.
authors.forename: Parames C
authors.initials: PC
authors.lastname: Sil
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D001151:Arsenic / Q000378:metabolism / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D059865:Endoplasmic Reticulum Stress; D048049:Extracellular Signal-Regulated MAP Kinases; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009929:Organ Size; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D044004:Xanthones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D014874:Water Pollutants, Chemical; D044004:Xanthones; C013592:mangiferin; D048049:Extracellular Signal-Regulated MAP Kinases; D001151:Arsenic
keywords: Nrf 2; arsenic; hepatotoxicity; mangiferin; oxidative stress and ER stress