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Combination therapy with vitamin C and DMSA for arsenic-fluoride co-exposure in rats

Abstract

Introduction: Arsenic and fluoride are recognized globally as the most serious inorganic contaminants in drinking water. As there is no safe and effective treatment for the cases of fluoride poisoning and combined arsenic-fluoride toxicity thus present study was planned to assess (i) mechanism of combined exposure to arsenic and fluoride via biochemical and spectroscopic data (ii) effect of a thiol chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA) either individually or in combination with an antioxidant vitamin C in reversing arsenic-fluoride toxicity; and (iii) whether combination therapy enhances arsenic and fluoride removal from blood and soft tissues. Methods: Rats were exposed to arsenic (50 mg/l) and fluoride (50 mg/l) individually and in combination for 9 months and later received DMSA (50 mg/kg) via i.p. route and vitamin C (25 mg/kg) orally for 5 days. Biochemical parameters suggestive of alterations in heme synthesis pathway, oxidative stress in blood, liver and kidneys, and concentration of arsenic and fluoride in blood and soft tissues were studied. We also studied Infra red (IR) spectrum of DNA extracted from liver and kidney of normal and exposed animals. Results: It was found that chronic arsenic and fluoride exposure led to increased oxidative stress condition and impaired heme synthesis (67% inhibition in δ- aminolevulinic acid dehydratase activity and 38% increase in -aminolevulinic acid synthetase activity). Decreased antioxidant defense mechanism was marked by 2.25 folds increased concentration of Reactive Oxygen Species (ROS) and 28% decrease in Glutathione (GSH) level. Interstingly, concomitant exposure to arsenic and fluoride did not led to the antagonistic effects as the toxic effects were the same as seen during the invidual exposure to both the toxicants. It suggests that toxicity depends upon the dose and duration of exposure. Combination therapy with DMSA with vitamin C showed a better efficacy as compared to monotherapy in terms of reducing the arsenic and fluoride burden (more than 70% in blood and soft tissues) as well as reversal in the altered biochemical variables indicative of oxidative stress and tissue damage (80-85%). Infra red (IR) spectrum of DNA isolated from liver and kidney suggested that the treatment with vitamin C and DMSA had no beneficial effects in terms of reversing DNA damage. Conclusion: On the basis of the above observations, we suggest that combinational therapy of DMSA and vitamin C would be more effective in arsenic and/or fluoride toxicity however more detailed studies are required to address recoveries in DNA damage.

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Publication details

The article was received on 16 Jul 2018, accepted on 27 Jul 2018 and first published on 27 Jul 2018


Article type: Paper
DOI: 10.1039/C8MT00192H
Citation: Metallomics, 2018, Accepted Manuscript
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    Combination therapy with vitamin C and DMSA for arsenic-fluoride co-exposure in rats

    M. Mittal, S. Chatterjee and S. Flora, Metallomics, 2018, Accepted Manuscript , DOI: 10.1039/C8MT00192H

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