title: Arsenic-Induced Antioxidant Depletion, Oxidative DNA Breakage, and Tissue Damages are Prevented by the Combined Action of Folate and Vitamin B12.
abstract: Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C) metabolism and cellular methyl (-CH3) pool. The -CH3 group helps in arsenic disposition and detoxification of the biological systems. Vitamin B12 and folate, the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0 μg, respectively/100 g b.w. of rat for 28 days) to evaluate their combined efficacy in the protection from mutagenic DNA-breakage and tissue damages. The selected tissues like intestine (first-pass site), liver (major xenobiotic metabolizer) and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6 ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions were monitored. Our earlier studies on arsenic-exposed humans can correlate carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of physiological/therapeutic dose of vitamin B12 and folate protected the rodents significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay) and hepatic and renal tissue degeneration (histo-architecture, HE staining). The level of arsenic-induced free-radical products (TBARS and conjugated diene) was significantly declined by the restored actions of several antioxidants viz. urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase, transaminases, urea and creatinine (hepatic and kidney toxicity marker), and lactate dehydrogenase (tissue degeneration marker) were significantly impaired in the arsenic-fed group. But a significant protection was evident in the vitamin-supplemented group. In conclusion, the combined action of folate and B12 results in the restitution in the 1C metabolic pathway and cellular methyl pool. The cumulative outcome from the enhanced arsenic methylation and antioxidative capacity was protective against arsenic induced mutagenic DNA breakages and tissue damages.
authors: Department of Biochemistry, Cell and Molecular Therapeutics Laboratory, Oriental Institute of Science and TechnologyVidyasagar University, Midnapore, West Bengal, 721102, India.|Department of Biotechnology, Oriental Institute of Science and Technology, Vidyasagar University, Midnapore, West Bengal, 721102, India.|Department of Biomedical Laboratory Science and Management, (UGC Innovative Department), Vidyasagar University, Midnapore, West Bengal, 721102, India.
authors: Nirmallya
authors: N
authors: Acharyya
authors: Department of Biomedical Laboratory Science and Management, (UGC Innovative Department), Vidyasagar University, Midnapore, West Bengal, 721102, India.
authors: Bimal
authors: B
authors: Deb
authors: Department of Biomedical Laboratory Science and Management, (UGC Innovative Department), Vidyasagar University, Midnapore, West Bengal, 721102, India.
authors: Sandip
authors: S
authors: Chattopadhyay
authors: Department of Biochemistry, Cell and Molecular Therapeutics Laboratory, Oriental Institute of Science and TechnologyVidyasagar University, Midnapore, West Bengal, 721102, India. maitism@yahoo.co.in.|Department of Biotechnology, Oriental Institute of Science and Technology, Vidyasagar University, Midnapore, West Bengal, 721102, India. maitism@yahoo.co.in.|Epidemiology and Human Health Division, Agricure Biotech Research Society, Midnapore, 721101, India. maitism@yahoo.co.in.
authors: Smarajit
authors: S
authors: Maiti
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001151:Arsenic / Q000633:toxicity*; D020261:Arsenic Poisoning / Q000378:metabolism* / Q000517:prevention & control*; D020552:Comet Assay; D004249:DNA Damage; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008315:Malondialdehyde / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D014805:Vitamin B 12 / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D009153:Mutagens; D017392:Thiobarbituric Acid Reactive Substances; D014815:Vitamins; D008315:Malondialdehyde; D005492:Folic Acid; D001151:Arsenic; D014805:Vitamin B 12
keywords: Antioxidant systems; Arsenic; DNA breakage; Folate; Vitamin B12