title: Vitamin E supplementation protects oxidative stress during arsenic and fluoride antagonism in male mice.
abstract: Arsenic and fluoride are common environmental contaminants. Coexposure to these elements can occur through groundwater. We investigated the effects of sodium meta arsenite (50 mg/L in drinking water) and sodium fluoride (50 mg/L in drinking water) individually and in combination. Biochemical parameters suggestive of alterations in heme synthesis pathway, oxidative stress in liver and kidneys, and concentration of essential metals in blood and soft tissues were studied in Swiss albino male mice given the chemicals for 3 weeks. The possible beneficial effect of vitamin E administration (25 mg/kg, oral, alternate days after arsenic/fluoride exposure) on the above variables was investigated. Exposure to arsenic or fluoride caused a significant depletion in blood delta-aminolevulinic acid dehydratase (ALAD) activity, platelet counts (PLT), and glutathione (GSH) level. Blood white blood cell (WBC) counts also decreased. These changes were accompanied by increased reactive oxygen species (ROS) levels. Arsenic and fluoride exposure led to a significant depletion of super oxide dismutase (SOD) activity with no effect on catalase and glutathione peroxidase (GPx) activities. Combined exposure to these toxicants had no synergistic effect on blood ALAD activity and WBC counts, and the effects seen appeared to result predominantly from arsenic. Hepatic catalase activity, on the other hand, increased significantly on exposure to arsenic and fluoride. There was only moderate antagonistic effect on arsenic and fluoride concentration in blood and liver, and kidney arsenic concentration was less pronounced during coexposure compared with arsenic alone. Interestingly, fluoride concentration showed less pronounced uptake during concomitant exposure compared with fluoride exposure alone. Vitamin E supplementation during coexposure to arsenic and fluoride provided only moderate recovery in the altered antioxidant enzymes and in depleting ROS level, but the altered essential metal concentration, particularly calcium level, responded more favorably to vitamin E administration. It can be concluded from the current study that (i) coadministration of arsenic and fluoride was less toxic to the animals compared with individual toxic effects of these toxicants, and (ii) vitamin E supplementation during coexposure had only limited additional beneficial effects in restoring altered biochemical variables, maintaining pro-oxidant/antioxidant balance, and reducing body arsenic store but plays a significant role in maintaining essential metal balance.
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India.
authors.forename: Megha
authors.initials: M
authors.lastname: Mittal
authors.forename: S J S
authors.initials: SJ
authors.lastname: Flora
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D018053:Arsenites / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D002118:Calcium / Q000097:blood / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003300:Copper / Q000097:blood / Q000378:metabolism; D005978:Glutathione / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007958:Leukocyte Count; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010976:Platelet Count; D000623:Porphobilinogen Synthase / Q000097:blood; D017382:Reactive Oxygen Species / Q000378:metabolism; D017670:Sodium Compounds / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D012969:Sodium Fluoride / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D015032:Zinc / Q000097:blood / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D018053:Arsenites; D017382:Reactive Oxygen Species; D017670:Sodium Compounds; D014874:Water Pollutants, Chemical; C017947:sodium arsenite; D003300:Copper; D012969:Sodium Fluoride; D002374:Catalase; D013482:Superoxide Dismutase; D000623:Porphobilinogen Synthase; D005978:Glutathione; D024502:alpha-Tocopherol; D015032:Zinc; D002118:Calcium