Positive effects of Vitamin C in arsenic trioxide and sodium fluoride induced genotoxicity and oxidative stress in mice in vivo

Document Type : Original Research Paper

Authors

1 Laboratory of Genetic Toxicology and Environmental Health, Department of Life Science and Bioinformatics, Assam University, Silchar-788011, Assam, India.

2 Cell Biology and Genetic Toxicology Laboratory, Department of Genetics, University of Calcutta, Kolkata-700019, India.

10.7508/pj.2015.04.009

Abstract

The aim of the present study was to evaluate Vitamin C (VC) as a potent natural antioxidant to mitigate the genotoxic effects of Arsenic trioxide and sodium fluoride in Swiss albino mice in vivo. The study was divided into eight groups consisting of control treated with normal saline (Group I), Group II, III, IV, V, VI, VII and the VC group with only Vitamin C (500 mg/kgbw). Arsenic trioxide (4 mg/kgbw) and Sodium fluoride (8 mg/kgbw) were administered singly, as well as in combination to swiss albino mice, with and without VC. In this study, the genotoxic effect of arsenic (As) and fluoride (F) in mice using comet, chromosomal aberration and lipid peroxidation assay was investigated. The results revealed that VC efficiently ameliorates the genotoxic effect of As and F by increasing the frequency of chromosomal aberrations and primary DNA damage along with increased malondialdehyde (MDA) level. In conclusion, VC mitigates the genotoxic effects of the two well-known water contaminants (As and F) effectively and efficiently at the given concentration in vivo.

Keywords


Aardema, M.J., Gibson, D.P. and LeBoeuf, R.A. (1989). Sodium fluoride-induced chromosome aberrations in different stages of the cell cycle: a proposed mechanism. Mutat. Res., 223, 191-203.
Abernathy, C., Liu, Y., Longfellow, D., Aposhian, H., Beck, H., Fowler, B., Goyer, R., Menzer, R., Rossman, T., Thompson, C. and Waalkes, M. (1999). Arsenic: health effects, mechanisms of action and research issues. Environ. Health Perspect., 107, 593–597.
An, Y., Gao, Z., Wang, Z., Yang, S., Liang, F., Feng, Y., Kato, K., Nakano, M., Okada, S. and Yamanaka, K. (2004). Immunohistochemical analysis of oxidative DNA damage in arsenic-related human skin samples from arsenic-contaminated area of China. Cancer Lett., 214 (1), 11–18.
Aposhian, H. V. (1989). Biochemical toxicology of arsenic. Rev. Biochem. Toxicol., 10, 265–299.
ATSDR. (2003). Toxicological Profile for Fluorides, Hydrogen Fluoride and Fluorine.US Departmental of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Research. Toxicological Profile for Arsenic.
ATSDR. (2005). Toxicological Profile for Arsenic. US Departmental of Health and Human Services, Public Health Service, Atlanta, GA.
Barroso, M.P., Diaz, C.G., Lluch, G.L., Malagon, M.M., Crane, F.L. and Navas, P. (1997). Ascorbate andα-tocopherol prevent apoptosis induced by serum removal independent of Bcl-2. Archiv. Biochem. Biophys., 343, 243–248.
Burton, G.W., Joyce, A. and Ingold, K.U. (1983). Is vitamin E the only lipid-soluble, chain-breaking antioxidant in human blood plasma and erythrocyte membranes? Arch. Biochem. Biophys., 221, 281-90.
Chen, J., Chen, X., Yang, K., Xia, T. and Xie, H. (2002). Studies on DNA damage and apoptosis in rat brain induced by fluoride. Chinese Journal of Preventive Medicine, 36 (4), 222–224.
Crespi, C.L., Seixas, G.M., Turner, T. and Penman, B.W. (1990). Sodium fluoride is a less efficient human cell mutagen at low concentrations. Environ. Mol. Mutagen., 15, 71-77.
Cui, C.G. and Liu, Z.H. (1988). Chemical speciation and distribution of arsenic in water, suspended solids and sediment of Xiangjiang river. China Sci. Total Environ., 77, 69–72.
Dunkelberg, H., Luthin, S., Birkenkamp, P. and Gebel, T. (1998). Arsenic (III), but not antimony, induces DNA–protein cross-links. Anticancer Res., 18, 4253–4258.
Giri, A., Khynriam, D. and Prasad, S.B. (1998). Vitamin C mediated protection on cisplatin induced mutagenicity in mice. Mutat. Res., 421, 139–148.
Giri, S., Mazumdar, M. and Roy, D.L. (2008). Effects of low dose radiation and vitamin C treatment on chloroquine-induced genotoxicity in mice. Environmental and Molecular Mutagenesis, 49, 488-495.
Goering, P., Aposhian, H., Mass, M., Cebrián, M., Beck, B. and Waalkes, M. (1999).The enigma of arsenic carcinogenesis: role of metabolism. Toxicol. Sci., 49, 5–14.
Harrisson, J.W.E., Packman, E.W. and Abbott, D.D. (1958). Acute oral toxicity and chemical and physical properties of arsenic trioxides. Arch. Ind. Health, 17, 118–123.
Hayashi, M., Kishi, M., Sofuni, T. and Ishidate, M. Jr. (1988). Micronucleus test in mice on 39 food additives and eight miscellaneous chemicals. Food Chem.Toxicol., 26, 487–500.
He, L.F. and Chen, J.G. (2006). DNA damage, apoptosis and cell cycle changes induced by fluoride in rat oral mucosal cells and hepatocytes.World J.Gastroenterol., 12, 1144–1148.
Hindmarsh, J.T. and Mc Curdy, R.F. (1986). Clinical and environmental aspects of arsenic toxicity. CRC Crit. Rev. Clin. Lab. Sci., 23, 315–319.
Huang, C., Ma, W.Y., Li, J. and Dong, Z. (1999). Arsenic induces apoptosis through a c-junNH2-terminal kinase-dependent, p53-independent pathway. Cancer Res., 59, 3053–3058.
IARC. (1987). IARC Monographs on the Evaluation of Carcinogenic Risks of Chemicals to Humans: Overall Evaluations of Carcinogenicity, An Updating of IARC Monographs, 7 (1–42), World Health Organization, IARC, Lyon.
Ishaq, M., Rao Visweswara, K., Ahuja, R.Y., Jamil, Kaiser, Danadevi, K. and Banu, S.B. (2001). In vivo genotoxic effect of arsenic trioxide in mice using comet assay. Toxicology, 162,171-177.
Jeji, J., Sharma, R., Jolly, S.S. and Pamnani, S. (1985). Implication of glutathione in endemic fluorosis. Fluoride, 18, 117–119.
Jhala, D. D., Chinoy, N. J. and Rao, M.V. (2008). Mitigating effects of some antidotes on fluoride and arsenic induced free radical toxicity in mice ovary. Food Chem. Toxicol., 46 (3), 1138–1142.
Kaul, R.D. and Susheela, A.K. (1974). Evidence of muscle fibre degeneration in rabbits treated with sodium fluoride. Fluoride, 7, 177–181.
Kreppel, H., Bauman, J.W., Liu, J., Mc Kim, J.M. and Klaassen, C.D. (1993). Induction of metallothionein by arsenicals in mice. Fundam. Appl. Toxicol., 20, 184–189.
Krishna, G. and Hayashi, M. (2000). In vivo rodent micronucleus assay: protocol, conduct and data interpretation. Mutat. Res., 455, 155–166.
Krishna, G., Nath, J. and Ong, T. (1986). Inhibition of cyclophosphamide and Mitomycin C-induced sister chromatid exchanges in mice by vitamin C. Cancer Res., 46, 2670-2674.
Li, Y., Dunipace, A.J. and Stookey, G.K. (1987). Lack of genotoxic effects of fluoride in the mouse bone‐marrow micronucleus test. J. Dent. Res.,66, 1687–1960.
Li, Y., Liang, C.K., Katz, B.P., Brizendine, E.J. and Stookey, G.K. (1995). Long-term exposure to fluoride in drinking water and sister chromatid exchange frequency in human blood lymphocytes. J. Dent. Res., 74, 1468–1474.
Liu, S.X., Athar, M., Lippai, I. and Waldren, T.K. (2001). Induction of oxyradicals by arsenic: implication for mechanism of genotoxicity. Proc. Natl. Acad. Sci., 98, 1643–1648.
Luchtrath, H. (1972). Cirrhosis of the liver in chronic arsenical poisoning. German Med. Mon., 2, 127.
Martin, G.R., Brown, K.S., Matheson, D.W., Lebowitz, H., Singer, L. and Ophaug, R. (1979). Lack of cytogenetic effects in mice or mutations in Salmonella receiving sodium fluoride. Mutat. Res., 66, 159–167.
Menzel, D. and Rasmussen, R. (1997). Variation in arsenic-induced sister chromatid exchange in human lymphocytes and lymphoblastoid cell lines. Mutat. Res., 386, 299–306.
Mobio, T., Baudrimont, I., Sanni, A., Shier, T.W., Saboureau, D., Dano, S.D., Udeno, Y., Steyn, P.S. and Creppy, E.E. (2000). Prevention by Vitamin E of DNA fragmentation and apoptosis induced by fumonisin B1 in C6 glioma cells. Archiv. Toxicol., 74, 112–119.
Monteiro, H.P. and Stern, A. (1996). Redox regulation of tyrosine phosphorylation-dependent signal transduction pathways. Free. Radic. Biol. Med., 21, 323–333.
Mukherjee, R.N. and Sobels, F.A. (1968). The effects of sodium fluoride and iodoacetamide on mutation induction by x-irradiation in mature spermatozoa of Drosophila. Mutat. Res.,6, 217-225.
Naik, R.S., Mujumdar, A.M. and Ghaskadbi, S. (2004). Protection of liver cells from ethanol cytotoxicity by curcumin in liver slice culture in vitro. J. Ethnopharmacol., 95, 31-37.
NAS. (1999). Arsenic in Drinking water. Natl. Acad. Press, Washington, DC.
Nefic, H. (2001). Anticlastogenic effect of Vitamin C on cisplatin induced chromosome aberrations in human Iymphocyte cultures. Mutat. Res., 498, 89-98.
NRC. (1999). Arsenics in the Drinking Water, National Academy Press, Washington, DC.
Ochi, T., Nakajima, F., Sakurai, T., Kaise, T. and Oya-Ohta, Y. (1996). Dimethylarsinic acid causes apoptosis in HL-60 cells viainter-action with glutathione. Archiv. Toxicol., 70, 815–821. Odin, A. P. (1997). Vitamins as antimutagens: advantages and some possible mechanisms of antimutagenic action. Mutat. Res., 386, 39-67.
Ostrosky-Wegman, P., Gonsebatt, M. and Vega, L. (1995). Aneugenic effect of sodium arsenite on 
human lymphocytes in vitro: an individual susceptibility effect detected. Mutat. Res., 334, 365–373. Panneerselvam, C., Shila, S., Anusuyadevi, M. and Ramanathan, K. (2005). Ascorbic acid and α-tocopherol as potent modulators of apoptosis on arsenic induced toxicity in rats. Toxicology Letters, 156, 297-306. Pant, H, H. and Rao, V, M. (2010). Evaluation of in vitro anti-genotoxic potential of melatonin against arsenic and fluoride in human blood cultures. Ecotoxicology and Environmental Safety, 73, 1333-1337. Partridge, A., Huang, S.X.L., Hernandez-Rosa, E., Davidson, M.M. and Hei, T.K. (2007). Arsenic induced mitochondrial DNA damage and altered mitochondrial oxidative function: implications for genotoxic mechanisms in mammalian cells. Cancer Res., 67, 5239–5247. Pati, P.C. and Bhunya, S.P. (1987).Genotoxic effect of an environmental pollutant, sodium fluoride, in mammalian in vivo test system.Caryologia,40, 79–87. Pekkanen, J., Paldy, A., Kurttio, P. andMäki-Paakkanen, J. (1998). Association between the clastogenic effect in peripheral lymphocytes and human exposure to arsenic through drinking water. Environ. Mol. Mutagen., 32, 301–313. Pillai, K.S., Mathai, A.T. and Deshmukh, P.B. (1988). Effect of subacute dosage of fluoride on male mice.Toxicol. Lett., 44, 21-29. Podder, S., Chattopadhyay, A. andBhattacharya, S. (2008). In vivo suppression by fluoride of chromosome aberrations induced by mitomycin‐cinmouse bone marrow cells. Fluoride, 41, 40–43. Podder, S., Chattopadhyaya, A. and Bhattacharya, S. (2011). Reduction in fluoride‐induced genotoxicity in mouse bone marrow cells after substituting high fluoride‐containing water with safe drinking water. J. Appl. Toxicol., 31, 703–705. Rao, V.M. and Tiwari, H. (2010). Curcumin supplementation protects from genotoxic effects of arsenic and fluoride. Food and Chemical Toxicology, 48, 1234-1238. Saralakumari, D. and Rao, R.P. (1991). Red cell membrane alterations in human chronic fluoride toxicity. Biochem. Int., 23, 639–648.
Shafiq-ur-Rehman (2003). Lead-exposed increase in movement behaviour and brain lipid peroxidation in fish. Journal of Environmental Science and Health, 38 (4), 631–643.
Shanthakumari, D., Srinivasalu S. and Subramanian, S. (2004). Effects of fluoride intoxication on lipid peroxidation and antioxidant status in experimental rats. Toxicology, 204, 219–228. Slacik-Erben, R. and Obe, G. (1976).The effect of sodium fluoride on DNA synthesis, mitotic indices and chromosomal aberrations in human leukocytes treated with Trenimon in vitro. Mutat. Res., 37, 253-266. Sollott, S.J., Juhaszova, M. and Zorov, D.B. (2006). Mitochondrial ROS-induced ROS release: an update and review. Biochim. Biophy. Acta, 1757, 509–517. Smerak, P., Polivkova, Z., Sestakova, H., Stetina, R., Barta, I., Langova, M., Turek, B. and Bartova, J. (2006). Antimutagenic effect of curcumin and its effect on the immune response in mice. Czech J. Food Sci., 24, 72–83. Straface, E., Santini, M.T., Donelli, G., Giacomoni, P.U. and Malorni, W. (1995). Vitamin E prevents UV B-induced cell blebbing and cell death in A431 epidermoid cells. Int. J. Radiat. Biol., 68, 579–587. Susheela, A.K. and Bhatnagar, M. (2002). Reversal of fluoride induced cell injury through elimination of fluoride and consumption of diet rich in essential nutrients and antioxidants. Mol. Cell. Biochem., 234, 335–340. Tice, R.R., Agurell, E., Anderson, D., Burlinson, B., Hartmann, A., Kobayashi, H., Miyamae, Y., Rojas, E., Ryu, J.C. and Sasaki, Y.F. (2000). Single cell gel / Comet assay: Guidelines for in vitro and in vivo genetic toxicology testing. Environ. Mol. Mutagen., 35, 206–221. Tsutsui, T., Suzuki, N. and Ohmori, M. (1984). Sodium fluoride-induced morphological and neoplastic transformation, chromosome aberrations, sister chromatid exchanges, and unscheduled DNA synthesis in cultured Syrian hamster embryo cells. Cancer Res., 44, 938-941. Wang, T.S., Kuo, C.H., Jan, K.Y. and Huang, H. (1996). Arsenite induces apoptosis in Chinese hamster ovary cells by generation of reactive oxygen species. J. Cell Physiol., 169, 256–267.
Zhang, M., Wang, A., Xia, T. and He, P. (2008). Effects of fluoride on DNA damage, S-phase cell-cycle arrest and the expression of NF-kappaB in primary cultured rat hippocampal neurons. Toxicol. Lett., 179, 1–5.