PROTECTIVE ROLE OF VITAMIN C AND E AGAINST SODIUM ARSENATE INDUCED CHANGES IN DEVELOPING KIDNEY OF ALBINO MICE
AbstractBackground: Arsenic is a teratogenic agent present in the environment as oxides and arsenate andhumans are exposed to it through contaminated drinking water, food, soil and air. This investigationwas undertaken to evaluate protective role of Vitamin C and E against teratogenic injury produced bysodium arsenate in developing kidney of the mouse. Methods: Twenty-four pregnant albino mice ofBALB/c strain, were randomly divided into 4 groups of 6 each: A1, A2, A3 and A4. Group A1 served asthe control and received weight related distilled water by intra-peritoneal (I/P) injection, group A2 wasgiven a single doses of 35 mg/kg on 8th GD whereas groups A3 and A4 were treated with Vitamin C andE by IP injection, 9 mg/kg/day and 15 mg/kg/day respectively, starting from 8th day and continued forthe rest of the pregnancy period. The foetal kidneys were weighed and histological studies carried outincluding micrometry on different components of nephron. Results: Sodium arsenate toxicitymanifested as an increase in weight of the kidneys, wider nephrogenic zone and significant reduction inthe mean of number of mature renal corpuscles as compared to the control group (p<0.000). There weremoderate to severe necrotic and degenerative changes in proximal and distal convoluted tubules;glomeruli were hypercellular, the Bowman’s spaces were obliterated. There was a statisticallysignificant difference in mean diameter of renal corpuscles of group A2 when compared with groupsA1, A3 and A4, (p<0.000). Conclusions: The findings implied that groups receiving Vitamin C and Ealong with sodium arsenate showed an overall improvement in all parameters, indicating the protectiverole of Vitamin C and E against arsenic induced teratogenicity in developing kidney and are safe to useduring pregnancy without deleterious effect on human conspectuses in arsenic exposed areas.Keywords: Arsenic, teratogenic, ascorbic acid, nephrogenesis.
Indian Council of Medical Research (ICMR). Foetotoxic
evaluations of environmental agents. New Delhi: National
Pediculosis Association; 2006.
Caravati EM. Arsenic and Arsine Gas. In: Dart RC, editor.
Medical Toxicology. Philadelphia: Lippincott Williams and
MSDS. Sodium Arsenate Heptahydrate. USA: Mallinckrodt
Patrick L. Toxic Metals and Antioxidants: Part II. The Role
of Antioxidants in Arsenic and Cadmium Toxicity.
Alternative Medicine Review 2003;8(2):106–28.
Ratnaike RN. Acute and chronic arsenic toxicity. Postgrad
Med J 2003;79:391–6.
U.S. Environmental Protection Agency. Arsenic Compounds.
Air Toxic Website, 2005.
Krogt PVD. Arsenicum Arsenic. Elementymol Elements
Milton AH, Smith W, Rahman B, Hasan Z, Kulsum U, Dear
K et al. Chronic Arsenic Exposure and Adverse Pregnancy
Outcomes in Bangladesh. Epidemiology 2005;16(1):82–6.
Waalkes MP, Ward JM, Diwan BA. Induction of tumors of
the liver, lung, ovary and adrenal in adult mice after brief
maternal gestational exposure to inorganic arsenic:
promotional effects of postnatal phorbol ester exposure on
hepatic and pulmonary, but not dermal cancers
Milton AH, Hasan Z, Shahidullah SM, Sharmin S, Jakariya
MD, Rahman M et al. Association between nutritional status
and arsenicosis due to chronic arsenic exposure in
Bangladesh. Int J Environ Health Res 2004;14(2):99–108.
Mead MN. Arsenic: In Search of an Antidote to a Global
Poison. Environ Health Perspect 2005;113(6):A378–86.
J Ayub Med Coll Abbottabad 2009;21(4)
Fresh water and Toxic Programme, WWF-Pakistan. Pakistan’s
Waters at Risk. Water and Health Related Issues in Pakistan and
Key Recommendations. Feb 2007: www.wwfpark.org
Alam MZ, Rahman MM. Accumulation of Arsenic in Rice
Plant from Arsenic Contaminated Irrigation Water and Effect
on Nutrient Content. In: Ahmed F, Ali MA, Adeel Z, editors.
BUET-UNU International Symposium of Fate of Arsenic In
The Environment;2003 Sep23; Dhaka, Bangladesh.
Ahmad SA, Sayed MH, Barua S, Khan MH, Faruquee MH,
Jalil A, et al. Arsenic in Drinking Water and Pregnancy
Outcomes. Environ Health Perspect 2001;109(6):629-31.
Stump DG, Holson JF, Fleeman TL, Nemee MD, Farr CH.
Comparative Effects of Single Intraperitoneal or Oral Doses
of Sodium Arsenate or Arsenic Trioxide During In Utero
Development. Teratology 1999;60:283–91.
Solhaug MJ, Bolger PM, Jose PA. The Developing Kidney
and Environmental Toxins. Paediatrics 2004;113(4):1084-91
Duthie GG. Vitamin E and its Antioxidant role in relation to
other dietary components. In Garrow GS, James WPT,
editors. Human Nutrition and Dietetics. Churchill
Livingstone; 2005.p. 226–35.
Malafa MP, Fokum FD, Mowlavi A, Abusief M, King M.
Vitamin E inhibits melanoma growth in mice. Surgery 2002;
Mach M, Ujhazy E, Dubovicky M, Kovacovsky P, Navarova
J. High-dose Vitamin E supplementation in phenytoininduced intrauterine hypoxia: Teratological study. Biologia,
Kathleen A. Head ND. Ascorbic Acid in the Prevention and
Treatment of Cancer. Alternative Medicine Review
Liu J, Liu Y, Goyer RA, Achanzar W, Waalkes MP.
Metallothionein-I/II null mice aremore sensitive than wildtype mice to the hepatotoxic and nephrotoxic effects of
chronic oral or injected inorganic arsenicals. Toxicol Sci
Flora SJS. Nutritional components modify metal absorption,
toxic response and chelation therapy. J Environ Med
Saxen L. The Developing Kidney in Toxicity Tests. In:
Bourdeau P et al. Short- term Toxicity Tests for Nongenotoxic Effects. John Wiley & Sons Ltd;1990.135–53.
Dickinson H, Walker DW, Cullen-Mcewen L, Wintour EM,
Moritz K. The spiny mouse (Acomys cahirinus) completes
nephrogenesis before birth. Am J Physiol Renal Physiol
Wintour E.M, Moritz K.M, Johnson K, Ricardos, Samuel CS,
Dodic M. Reduced nephron number in adult sheep,
hypertensive as a result of prenatal glucocorticoid treatment.
J physiol 2003;549:929–35.
Govan DT, Macfarlane PS, Callander R. Genitourinary
system. In: Horne J, Jones D, Mckillo PH, Arnott N.
Pathology illustrated. 4th Ed. New York: Churchill
Livingstone; 1996. 597–692.
Peraza MA, Cromey DW, Carolus B, Carter DE, Gandolfi
AJ. Morphological and functional alterations in human
proximal tubular cell line induced by low level inorganic
arsenic: evidence for targeting of mitochondria and initiated
apoptosis. Journal of Applied Toxicology 2006;26:356–67.