Folic acid or combination of folic acid and vitamin B₁₂ prevents short‐term arsenic trioxide‐induced systemic and mitochondrial dysfunction and DNA damage

Abstract

The effect of folic acid and folic acid + vitamin B12 supplementation upon short‐term arsenic‐induced systemic and pancreatic islet cell mitochondria oxidative stress was investigated in male rats. Arsenic trioxide was administered orally at a dose of 3 mg kg body weight−1 day−1 for 30 days, and folic acid and vitamin B12 were administered at a dose of 36 and 0.63 μg kg body weight−1 day−1, respectively, for 30 days. Compared to control, arsenic‐treated group showed a significant increase in the levels of systemic oxidative markers, malondialdehyde (MDA), nitric oxide (NO), and hydroxyl radical (OH−) formation, which were found decreased significantly after supplementation either with folic acid or a combination of folic acid + vitamin B12. Similar supplementations were found effective against arsenic‐induced oxidative marker changes (MDA, NO, and OH−) in pancreatic islet cell mitochondria. Also, low activities of antioxidant defense enzymes such as superoxide dismutase and catalase, and level of antioxidant glutathione, all could regain significantly on supplementations both against systemic and islet cell mitochondria oxidative stress. Results of agarose‐gel electrophoresis of DNA from lymphocytes and islet cells of arsenic‐exposed rats showed DNA smearing, which could be reduced with simultaneous administration either with folic acid or a combination of folic acid + vitamin B12. Significantly, similar supplementations were found effective in increasing the urinary clearance of arsenic. Together, these results indicate that folic acid and vitamin B12 may be effective to reduce the arsenic‐induced damage at molecular target level. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.

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