The Role of Vitamin C in Vanadyl-Sulfate-Induced Nephrotoxicity and Hepatotoxicity

Document Type : Original Article (s)

Authors

1 Student of Medicine, Water and Electrolytes Research Center AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

2 Water and Electrolytes Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Professor, Water and Electrolytes Research Center AND Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Associate Professor, Water and Electrolytes Research Center AND Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

5 Professor, Department of Pathology, School of Medicine , Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Vanadium (V) is a candidate to decrease the serum level of glucose in diabetic animal model. However, it affects the lipid peroxidation and antioxidant activity so could make nephrotoxicity and hepatotoxicity. In this study, the protective role of vitamin C as an antioxidant on nephrotoxicity and hepatotoxicity induced by vanadyl sulfate was investigated.Methods: This study was designed in 2 protocols. There were 3 groups in protocol 1 that received saline (group 1), saline daily for 7 days plus single dose of vanadyl sulfate (50 mg/kg intraperitoneally) in day 2 (group 2), or vitamin C (250 mg/kg intraperitoneally) daily for 7 days and single dose of vanadyl sulfate (group 3). There were 2 groups in protocol 2 that received saline plus single dose of vanadyl sulfate (50 mg/kg intraperitoneally) in day 2 (group 4) or vitamin C (250 mg/kg intraperitoneally) daily for 2 days plus single dose of vanadyl sulfate (group 5). At the end of experiment, blood samples were collected to measure serum level of blood urea nitrogen (BUN), creatinine (Cr), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP), and all animals were sacrificed for histopathology investigation and determination of kidney tissue damage score (KTDS).Findings: In protocol 1, BUN/Cr ratio, kidney weight (KW), and KTDS decreased significantly in vanadyl sulfate plus vitamin C group in comparison with vanadyl sulfate plus saline group (P < 0.05). In addition, serum level of AST and ALP significantly decreased in vanadyl sulfate plus vitamin C group. In protocol 2, not only similar results were not observed, but also vitamin C increased the side effects of vanadyl sulfate.  Conclusion: Administration of vitamin C as a potent antioxidant could decrease the vanadium-induced toxicity. So, as vanadyl sulfate can be used for diabetic model in laboratory, vitamin C can be useful to decrease the vanadium-induced nephrotoxicity and hepatotoxicity, too.

Keywords


  1. Poucheret P, Verma S, Grynpas MD, McNeill JH. Vanadium and diabetes. Mol Cell Biochem 1998; 188(1-2): 73-80.
  2. Battell ML, Yuen VG, McNeill JH: Treatment of BB rats with vanadyl sulphate. Pharmacol Commun 1992; 1: 291-301.
  3. Heyliger CE, Tahiliani AG, McNeill JH. Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 1985; 227(4693): 1474-7.
  4. Ramanadham S, Cros GH, Mongold JJ, Serrano JJ, McNeill JH. Enhanced in vivo sensitivity of vanadyl-treated diabetic rats to insulin. Can J Physiol Pharmacol 1990; 68(4): 486-91.
  5. Rossetti L, Lauglin MR. Correction of chronic hyperglycemia with vanadate, but not with phlorizin, normalizes in vivo glycogen repletion and in vitro glycogen synthase activity in diabetic skeletal muscle. J Clin Invest 1989; 84(3): 892-9.
  6. Yuen VG, Pederson RA, Dai S, Orvig C, McNeill JH. Effects of low and high dose administration of bis(maltolato)oxovanadium(IV) on fa/fa Zucker rats. Can J Physiol Pharmacol 1996; 74(9): 1001-9.
  7. Brichard SM, Bailey CJ, Henquin JC. Marked improvement of glucose homeostasis in diabetic ob/ob mice given oral vanadate. Diabetes 1990; 39(11): 1326-32.
  8. Brichard SM, Pottier AM, Henquin JC. Long term improvement of glucose homeostasis by vanadate in obese hyperinsulinemic fa/fa rats. Endocrinology 1989; 125(5): 2510-6.
  9. Llobet JM, Domingo JL. Acute toxicity of vanadium compounds in rats and mice. Toxicol Lett 1984; 23(2): 227-31.
  10. Talvitie NA, Wagner WD. Studies in vanadium toxicology. II. Distribution and excretion of vanadium in animals. AMA Arch Ind Hyg Occup Med 1954; 9(5): 414-22.
  11. Hosseini MJ, Shaki F, Ghazi-Khansari M, Pourahmad J. Toxicity of vanadium on isolated rat liver mitochondria: a new mechanistic approach. Metallomics 2013; 5(2): 152-66.
  12. Liu J, Cui H, Liu X, Peng X, Deng J, Zuo Z, et al. Dietary high vanadium causes oxidative damage-induced renal and hepatic toxicity in broilers. Biol Trace Elem Res 2012; 145(2): 189-200.
  13. Domingo JL. Vanadium and tungsten derivatives as antidiabetic agents: a review of their toxic effects. Biol Trace Elem Res 2002; 88(2): 97-112.
  14. Domingo JL, Gomez M, Sanchez DJ, Llobet JM, Keen CL. Toxicology of vanadium compounds in diabetic rats: the action of chelating agents on vanadium accumulation. Mol Cell Biochem 1995; 153(1-2): 233-40.
  15. Mongold JJ, Cros GH, Vian L, Tep A, Ramanadham S, Siou G, et al. Toxicological aspects of vanadyl sulphate on diabetic rats: effects on vanadium levels and pancreatic B-cell morphology. Pharmacol Toxicol 1990; 67(3): 192-8.
  16. Ginter E. Ascorbic acid in cholesterol metabolism and in detoxification of xenobiotic substances: problem of optimum vitamin C intake. Nutrition 1989; 5(6): 369-74.
  17. Noctor G, Foyer CH. Ascorbate and glutathione: Keeping active oxygen under control. Annu Rev Plant Physiol Plant Mol Biol 1998; 49: 249-79.
  18. Stahl W, Sies H. Antioxidant defense: vitamins E and C and carotenoids. Diabetes 1997; 46(Suppl 2): S14-S18.
  19. Suleiman JB, Eze ED, Momoh IJ, Usman W, Hedima NC, Zipele HM, et al. Ameliorative effect of vitamin C on serum liver enzymes in lead-induced toxicity in wistar rats. Journal of Science 2013; 3(1): 188-92.
  20. Antunes LM, Darin JD, Bianchi MD. Protective effects of vitamin c against cisplatin-induced nephrotoxicity and lipid peroxidation in adult rats: a dose-dependent study. Pharmacol Res 2000; 41(4): 405-11.
  21. Roomi MW, Kalinovsky T, Roomi NW, Rath M, Niedzwiecki A. Prevention of Adriamycin-induced hepatic and renal toxicity in male BALB/c mice by a nutrient mixture. Exp Ther Med 2014; 7(4): 1040-4.
  22. Risso-de FC, Orsini N, de Sousa G, Rahmani R. Cadmium-induced apoptosis through the mitochondrial pathway in rainbow trout hepatocytes: involvement of oxidative stress. Aquat Toxicol 2004; 69(3): 247-58.
  23. Phillips TD, Nechay BR, Heidelbaugh ND. Vanadium: Chemistry and the kidney. Fed Proc 1983; 42(13): 2969-73.
  24. Al-Bayati MA, Xie Y, Mohr FC, Margolin SB, Giri SN. Effect of pirfenidone against vanadate-induced kidney fibrosis in rats. Biochem Pharmacol 2002; 64(3): 517-25.
  25. de la Torre A, Granero S, Mayayo E, Corbella J, Domingo JL. Effect of age on vanadium nephrotoxicity in rats. Toxicol Lett 1999; 105(1): 75-82.
  26. Marouane W, Soussi A, Murat JC, Bezzine S, El Feki A. The protective effect of Malva sylvestris on rat kidney damaged by vanadium. Lipids Health Dis 2011; 10: 65.
  27. Zychlinski L, Byczkowski JZ. Inhibitory effects of vanadium pentoxide on respiration of rat liver mitochondria. Arch Environ Contam Toxicol 1990; 19(1): 138-42.
  28. Ocak S, Gorur S, Hakverdi S, Celik S, Erdogan S. Protective effects of caffeic acid phenethyl ester, vitamin C, vitamin E and N-acetylcysteine on vancomycin-induced nephrotoxicity in rats. Basic Clin Pharmacol Toxicol 2007; 100(5): 328-33.
  29. Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr 2003; 22(1): 18-35.
  30. Wenzel U, Nickel A, Kuntz S, Daniel H. Ascorbic acid suppresses drug-induced apoptosis in human colon cancer cells by scavenging mitochondrial superoxide anions. Carcinogenesis 2004; 25(5): 703-12.
  31. Nematbakhsh M, Pezeshki Z, Eshraghi-Jazi F, Ashrafi F, Nasri H, Talebi A, et al. Vitamin E, Vitamin C, or Losartan Is Not Nephroprotectant against Cisplatin-Induced Nephrotoxicity in Presence of Estrogen in Ovariectomized Rat Model. Int J Nephrol 2012; 2012: 284896.
  32. Ashrafi F, Nematbakhsh M, Safari T, Talebi A, Nasri H, Khazaei M, et al. A combination of vitamin C and losartan for cisplatin-induced nephrotoxicity in rats. Iran J Kidney Dis 2012; 6(5): 361-5.