• Faouzi Dahdouh
  • Salah Attalah
  • Djabar Mohamed Reda
  • Zine Kechrid Laboratory of Biochemistry and Applied Microbiology, Department of Biochemistry, Badji Mokhtar University, Annaba, Algeria


Objective: The aim of this study was to investigate the effect of vitamins C and E separately and in combination against nickel-induced alterations in haematological indices and kidney dysfunction.

Methods: Male Swiss albino mice were divided into eight equal groups: Control, vitamin C (Vit C), vitamin E (Vit E), vitamin C and vitamin E (Vit C+Vit E), nickel (Ni), nickel and vitamin C (Ni+Vit C), nickel and vitamin E (Ni+Vit E), and nickel plus vitamins C and E (Ni+Vit C+Vit E). Vitamin C (1g/l) was given to mice through their drinking water. Vitamin E (1g/kg) and nickel as nickel sulfate (2.7 mg/kg) were supplemented in diet for four weeks.

Results: Nickel caused a significant decrease in body weight, food and water consumption along with significant increase in the absolute and relative kidney weights. Haemoglobin, red blood cells count (RBC), hemoglobin (Hb) concentration, platelet counts (Plt) and packed cell volume (PCV) were significantly diminished, while white blood cells count (WBC) increased in nickel exposed mice. The renal damage induced by nickel was evidenced by a significant increase in the levels of serum urea, creatinine and uric acid. However, vitamins C and E in combination more significantly ameliorated the altered histopathological and biochemical changes in the kidney as well as hematological parameters of Ni intoxicated mice than either vitamin C or E.

Conclusion: The study showed that vitamin C and E combination effectively attenuated Ni-induced heamatotoxicity and nephrotoxiicty in mice.

Keywords: Nickel, Vitamins C, Vitamin E, Heamatotoxicity, Kidney injury, Histopathology


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De Brouwere K, Buekers J, Cornelis C, Schlekat CE, Oller AR. Assessment of indirect human exposure to environmental sources of nickel: oral exposure and risk characterization for systemic effects. Sci Total Environ 2011;419:25-36.

Leblanc JC, Guérin T, Noël L, Calamassi-Tran G, Volatier JL, Verger P. Dietary exposure estimates of 18 elements from the 1st french total diet study. Food Addit Contam 2005;22:624-41.

Cempel M, Janicka K. Distribution of nickel, zinc, and copper in rat organs after oral administration of nickel (II) chloride. Biol Trace Elem Res 2002;90:215-26.

Bardack S, Dalgard CL, Kalinich JF, Kasper CE. Genotoxic changes to rodent cells exposed in vitro to tungsten, nickel, cobalt and iron. Int J Environ Res Public Health 2014;11:2922-40

Boulila S, Elfeki A, Oudadesse H, Elfeki H. Substitution effects of a carbonated hydroxyapatite biomaterial against intoxication chloride nickel-exposed rats. Toxicol Mech Methods 2015;25:155-65.

Jadhav SH, Sarkar SN, Patil RD, Tripathi HC. Effects of subchronic exposure via drinking water to a mixture of eight water-contaminating metals: a biochemical and histopathological study in male rats. Arch Environ Contam Toxicol 2007;53:667-77.

Permenter MG, Lewis JA, Jackson DA. Exposure to nickel, chromium, or cadmium causes distinct changes in the gene expression patterns of a rat liver derived cell line. PLoS One 2011;6:e27730. Doi:10.1371/journal.pone.0027730. [Article in Press]

Huang X, Zhuang Z, Frenkel K, Klein CB, Costa M. The role of nickel and nickel-mediated reactive oxygen species in the mechanism of nickel carcinogenesis. Environ Health Perspect 1994;102 Suppl 3:281-4.

Tikare SN, Yendigeri S, Gupta AD, Dhundasi SA, Das KK. Effect of garlic (Allium sativum) on hematology and erythrocyte antioxidant defense system of albino rats exposed to heavy metals (nickel II & chromium VI). Indian J Physiol Pharmacol 2012;56:137-46.

Adjroud O. The toxic effects of nickel chloride on liver, erythropoiesis, and development in Wistar albino preimplanted rats can be reversed with selenium pretreatment. Environ Toxicol 2013;28:290-8.

Tkeshelashvili LK, Tsakadze KJ, Khulusauri OV. Effect of some nickel compounds on red blood cell characteristics. Biol Trace Elem Res 1989;21:337-42.

Das KK, Saha S. L-ascorbic acid and α tocopherol supplementation and antioxidant status in nickel or lead-exposed rat brain tissue. J Basic Clin Physiol Pharmacol 2010;21:325-46.

Emilie P, Maurice H, Gilles C, Joel P, Jacques M, Dalila C. Oxidative stress and dystrophy facioscapulohumeral: effects of vitamin C, vitamin E, zinc gluconate and selenomethionine supplementation. Free Radical Biol Med 2014;75 Suppl 1:S14.

Pascoe GA, Fariss MW, Olafsdottir K, Reed DJ. A role of vitamin E in protection against cell injury. Maintenance of intracellular glutathione precursors and biosynthesis. Eur J Biochem 1987;166:241-7.

Cathcart RF. 3rd. Vitamin C: the nontoxic, non-rate-limited, antioxidant free radical scavenger. Med Hypotheses 1985;18:61-77.

Das KK, Buchner V. Effect of nickel exposure on peripheral tissues: role of oxidative stress in toxicity and possible protection by ascorbic acid. Rev Environ Health 2007;22:157-73.

Hattiwale SH, Saha S, Yendigeri SM, Jargar JG, Dhundasi SA, Das KK. Protective effect of L-ascorbic acid on nickel-induced pulmonary nitrosative stress in male albino rats. Biometals 2013;26:329-36.

Kasprzak KS, Diwan BA, Kaczmarek MZ, Logsdon DL, Fivash MJ, Salnikow K. Effects of ascorbic acid on carcinogenicity and acute toxicity of nickel subsulfide, and on tumor transplants growth in gluconolactone oxidase knock-out mice and wild-type C57BL mice. Toxicol Appl Pharmacol 2011;257:32-7.

Yildirim O, Büyükbingöl Z. In vivo effect of vitamin C with cobalt on oxidative stress in experimental diabetic rat kidney. Diabetes Nutr Metab 2003;16:208-13.

Alberts DS, Peng YM, Moon TE. Alpha-Tocopherol pretreatment increases adriamycin bone marrow toxicity. Biomedicine 1978;29:189-91.

Schiffer RB, Sunderman FW Jr, Baggs RB, Moynihan JA. The effects of exposure to dietary nickel and zinc upon humoral and cellular immunity in SJL mice. J Neuroimmunol 1991;34:229-39.

Barbier O, Jacquillet G, Tauc M, Cougnon M, Poujeol P. Effect of heavy metals on, and handling by, the kidney. Nephron Physiol 2005;99:105-10.

Brucka-Jastrzębska E, Protasowicki M. Effects of cadmium and nickel exposure on haematological parameters of common carp, Cyprinus carpio L. Acta Ichthyol Piscatoria 2005;35:29–38.

Karabulut-Bulan O, Bolkent S, Yanardag R, Bilgin-Sokmen B. The role of vitamin C, vitamin E, and selenium on the cadmium-induced renal toxicity of rats. Drug Chem Toxicol 2008;31:413-26.

Muthu K, Krishnamoorthy P. Effect of Vitamin C and Vitamin E on mercuric chloride-induced reproductive toxicity in male rats. Biochem Pharmacol 2012;1:102.

Milton Prabu S, Shagirtha K, Renugadevi J. Quercetin in combination with vitamins (C and E) improves oxidative stress and renal injury in intoxicated cadmium rats. Eur Rev Med Pharmacol Sci 2010;14:903-14.

Obone E, Chakrabarti SK, Bai C, Malick MA, Lamontagne L, Subramanian KS. Toxicity and bioaccumulation of nickel sulfate in Sprague-Dawley rats following 13 w of subchronic exposure. J Toxicol Environ Health A 1999;57:379-401.

Chatterjee K, Chakarborty D, Majumdar K, Bhattacharyya A, Chatterjee GC. Biochemical studies on nickel toxicity in weanling rats--influence of vitamin C supplementation. Int J Vitam Nutr Res 1979;49:264-75.

Yin N, Yao X, Zhou Q, Faiola F, Jiang G. Vitamin E attenuates silver nanoparticle-induced effects on body weight and neurotoxicity in rats. Biochem Biophys Res Commun 2015;458:405-10.

Kong L, Tang M, Zhang T, Wang D, Hu K, Lu W, et al. Nickel nanoparticles exposure and reproductive toxicity in healthy adult rats. Int J Mol Sci 2014;15:21253-69.

Amudha K, Pari L. Beneficial role of naringin, a flavanoid on nickel-induced nephrotoxicity in rats. Chem Biol Interact 2011;193:57-64.

Appenroth D, Fröb S, Kersten L, Splinter FK, Winnefeld K. Protective effects of vitamin E and C on cisplatin nephrotoxicity in developing rats. Arch Toxicol 1997;71:677-83.

Atef M, Al-Attar. Antioxidant effect of vitamin E treatment on some heavy metals-induced renal and testicular injuries in male mice. Saudi J Biol Sci 2011;18:63-72.

Hosokawa S1, Nishitani H, Umemura K, Tomoyoshi T, Sawanishi K, Yoshida O. Relationship between serum nickel concentrations and anaemia in chronic haemodialysis patients. Int Urol Nephrol 1987;19:447-51.

Novelli EL, Rodrigues NL, Nagahashi AM, Sforcin JM, Ribas BO. Nickel chloride effects on erythrocyte generation of superoxide radical. Braz J Med Biol Res 1990;23:643-5.

Das Gupta A, Das SN, Dhundasi SA, Das KK. Effect of garlic (Allium sativum) on heavy metal (nickel II and chromium VI) induced alteration of serum lipid profile in male albino rats. Int J Environ Res Public Health 2008;5:147-51.

Klibet F, Boumendjel A, Khiari M, El Feki A, Abdennour C, Messarah M. Oxidative stress-related liver dysfunction by sodium arsenite: alleviation by pistacia lentiscus oil. Pharm Biol 2016;54:354-63.

Karmakar R, Bhattacharya R, Chatterjee M. Biochemical, a haematological and histopathological study in relation to time-related cadmium-induced hepatotoxicity in mice. Biometals 2000;13:231-9.



How to Cite

Dahdouh, F., S. Attalah, D. M. Reda, and Z. Kechrid. “EFFECT OF THE JOINT SUPPLEMENTATION OF VITAMIN C AND VITAMIN E ON NICKEL HEAMATOTOXICITY AND NEPHROTOXICITY IN MALE SWISS ALBINO MICE”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 8, no. 6, June 2016, pp. 234-9, https://journals.innovareacademics.in/index.php/ijpps/article/view/11443.



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