title: Arsenic-induced hepatic mitochondrial toxicity in rats and its amelioration by dietary phosphate.
abstract: The present study was aimed to test the hypothesis that inorganic phosphate may reduce arsenic toxicity by decreasing its intestinal transference. Co-administration of inorganic phosphate (6.56 M) and arsenic (6.07 mM) in the intestinal loops of rats, in situ, caused significant reduction of arsenic transference. Short-term arsenic exposure (3mg/kg body weight/day for 30 days) caused liver damage evidenced by activities of liver enzymes and necroinflammatory changes. These effects of arsenic were coupled with enhanced mitochondrial swelling, inhibition of cytochrome c oxidase, Ca(2+)-ATPase, a decrease in mitochondrial calcium content, changes in indices of hepatic mitochondrial oxidative stress and iNOS expression. Arsenic also increased hepatic caspase 3 activity and DNA fragmentation. All these apoptosis-related molecular changes caused by arsenic could be alleviated by supplementation with inorganic phosphate, which likely suggests a protective role of phosphate against arsenic-induced hepatotoxic changes.
authors.affiliation: Department of Physiology, Presidency College, Kolkata 700 073, India. sangita_presi@yahoo.com
authors.forename: Sangita
authors.initials: S
authors.lastname: Majumdar
authors.forename: Subhra
authors.initials: S
authors.lastname: Karmakar
authors.forename: Anasuya
authors.initials: A
authors.lastname: Maiti
authors.forename: Monalisa
authors.initials: M
authors.lastname: Choudhury
authors.forename: Aniruddha
authors.initials: A
authors.lastname: Ghosh
authors.forename: Asankur Sekhar
authors.initials: AS
authors.lastname: Das
authors.forename: Chandan
authors.initials: C
authors.lastname: Mitra
mesh_terms: D000818:Animals; D001151:Arsenic / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D020261:Arsenic Poisoning / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology* / Q000517:prevention & control*; D053938:DNA Fragmentation / Q000187:drug effects; D019587:Dietary Supplements; D017665:Hydroxyl Radical / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000473:pathology*; D051336:Mitochondrial Membranes / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010710:Phosphates / Q000627:therapeutic use*; D016226:Phosphorus, Dietary / Q000494:pharmacology*; D011042:Poisons / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D010710:Phosphates; D016226:Phosphorus, Dietary; D011042:Poisons; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D002374:Catalase; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D053148:Caspase 3; D001151:Arsenic