Nephro-Urology Monthly

Published by: Kowsar

Effect of Oral Administration of Magnesium on Cisplatin-Induced Nephrotoxicity in Normal and Streptozocin-Induced Diabetic Rats

Nepton Soltani 1 , 2 , Mehdi Nematbakhsh 3 , 4 , 5 , * , Fatemeh Eshraghi-Jazi 3 , Ardeshir Talebi 3 , 6 and Farzaneh Ashrafi 3 , 7
Authors Information
1 Research Center for Molecular Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, IR Iran
2 Department of Physiology, Hormozgan University of Medical Sciences, Bandar Abbas, IR Iran
3 Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, IR Iran
4 Department of Physiology, Isfahan University of Medical Sciences, Isfahan, IR Iran
5 Isfahan
6 Department of Clinical Pathology, Isfahan University of Medical Sciences, Isfahan, IR Iran
7 Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, IR Iran
Article information
  • Nephro-Urology Monthly: September 01, 2013, 5 (4); 884-890
  • Published Online: August 20, 2013
  • Article Type: Research Article
  • Received: April 17, 2013
  • Revised: May 13, 2013
  • Accepted: May 26, 2013
  • DOI: 10.5812/numonthly.11624

To Cite: Soltani N, Nematbakhsh M, Eshraghi-Jazi F, Talebi A, Ashrafi F. Effect of Oral Administration of Magnesium on Cisplatin-Induced Nephrotoxicity in Normal and Streptozocin-Induced Diabetic Rats, Nephro-Urol Mon. 2013 ; 5(4):884-890. doi: 10.5812/numonthly.11624.

Copyright © 2013, Nephrology and Urology Research Center. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background
2. Objectives
3. Materials and Methods
4. Results
5. Discussion
  • 1. Ward JM, Fauvie KA. The nephrotoxic effects of cis-diamminedichloroplatinum (NSC-119875) in male F344 rats. Toxicol Appl Pharmacol. 1976; 38: 535
  • 2. Lippman AJ, Helson C, Helson L, Krakoff IH. Clinical trials of cis-diamminedichloroplatinum (NSC-119875). Cancer Chemother Rep. 1973; 57(2): 191-200[PubMed]
  • 3. Madias NE, Harrington JT. Platinum nephrotoxicity. Am J Med. 1978; 65(2): 307-14
  • 4. Dentino M, Luft FC, Yum MN, Williams SD, Einhorn LH. Long term effect of cis-diamminedichloride platinum (CDDP) on renal function and structure in man. Cancer. 1978; 41(4): 1274-81[PubMed]
  • 5. Arany I, Safirstein RL. Cisplatin nephrotoxicity. Semin Nephrol. 2003; 23(5): 460-4[PubMed]
  • 6. Gonzales-Vitale JC, Hayes DM, Cvitkovic E, Sternberg SS. The renal pathology in clinical trials of cis-platinum (II) diamminedichloride. Cancer. 1977; 39(4): 1362-71[PubMed]
  • 7. Yao X, Panichpisal K, Kurtzman N, Nugent K. Cisplatin nephrotoxicity: a review. Am J Med Sci. 2007; 334(2): 115-24[DOI][PubMed]
  • 8. Daugaard G, Strandgaard S, Holstein-Rathlou NH, Frederiksen PL, Svendsen UG, Munck O, et al. The renal handling of sodium and water is not affected by the standard-dose cisplatin treatment for testicular cancer. Scand J Clin Lab Invest. 1987; 47(5): 455-9[PubMed]
  • 9. Gomez Campdera FJ, Gonzalez P, Carrillo A, Estelles MC, Rengel M. Cisplatin nephrotoxicity: symptomatic hypomagnesemia and renal failure. Int J Pediatr Nephrol. 1986; 7(3): 151-2[PubMed]
  • 10. Hans CP, Sialy R, BansalT DD. Magnesium deficiency and diabetes mellitus. Current Sci. 2002; 83(12): 1456-63
  • 11. Soltani N, Keshavarz M, Sohanaki H, Dehpour AR, Zahedi Asl S. Oral magnesium administration prevents vascular complications in STZ-diabetic rats. Life Sci. 2005; 76(13): 1455-64[DOI][PubMed]
  • 12. Soltani N, Keshavarz M, Sohanaki H, Zahedi Asl S, Dehpour AR. Relaxatory effect of magnesium on mesenteric vascular beds differs from normal and streptozotocin induced diabetic rats. Eur J Pharmacol. 2005; 508(1-3): 177-81[DOI][PubMed]
  • 13. Soltani N, Keshavarz M, Minaii B, Mirershadi F, Zahedi Asl S, Dehpour AR. Effects of administration of oral magnesium on plasma glucose and pathological changes in the aorta and pancreas of diabetic rats. Clin Exp Pharmacol Physiol. 2005; 32(8): 604-10[DOI][PubMed]
  • 14. Soltani N, Keshavarz M, Dehpour AR. Effect of oral magnesium sulfate administration on blood pressure and lipid profile in streptozocin diabetic rat. Eur J Pharmacol. 2007; 560(2-3): 201-5[DOI][PubMed]
  • 15. Hasanein P, Parviz M, Keshavarz M, Javanmardi K, Mansoori M, Soltani N. Oral magnesium administration prevents thermal hyperalgesia induced by diabetes in rats. Diabetes Res Clin Pract. 2006; 73(1): 17-22[DOI][PubMed]
  • 16. Shechter M, Sharir M, Labrador MJ, Forrester J, Silver B, Bairey Merz CN. Oral magnesium therapy improves endothelial function in patients with coronary artery disease. Circulation. 2000; 102(19): 2353-8[PubMed]
  • 17. de Araujo M, Andrade L, Coimbra TM, Rodrigues AC, Jr, Seguro AC. Magnesium supplementation combined with N-acetylcysteine protects against postischemic acute renal failure. J Am Soc Nephrol. 2005; 16(11): 3339-49[DOI][PubMed]
  • 18. Hans CP, Chaudhary DP, Bansal DD. Effect of magnesium supplementation on oxidative stress in alloxanic diabetic rats. Magnes Res. 2003; 16(1): 13-9[PubMed]
  • 19. Sarangarajan R, Cacini W. Early onset of cisplatin-induced nephrotoxicity in streptozotocin-diabetic rats treated with insulin. Basic Clin Pharmacol Toxicol. 2004; 95(2): 66-71[DOI][PubMed]
  • 20. Scott LA, Madan E, Valentovic MA. Attenuation of cisplatin nephrotoxicity by streptozotocin-induced diabetes. Fundam Appl Toxicol. 1989; 12(3): 530-9[PubMed]
  • 21. Valentovic MA, Scott LA, Madan E, Yokel RA. Renal accumulation and urinary excretion of cisplatin in diabetic rats. Toxicology. 1991; 70(2): 151-62[PubMed]
  • 22. Scott LA, Madan E, Valentovic MA. Influence of streptozotocin (STZ)-induced diabetes, dextrose diuresis and acetone on cisplatin nephrotoxicity in Fischer 344 (F344) rats. Toxicology. 1990; 60(1-2): 109-25[PubMed]
  • 23. Ashrafi F, Haghshenas S, Nematbakhsh M, Nasri H, Talebi A, Eshraghi-Jazi F, et al. The Role of Magnesium Supplementation in Cisplatin-induced Nephrotoxicity in a Rat Model: No Nephroprotectant Effect. Int J Prev Med. 2012; 3(9): 637-43[PubMed]
  • 24. Yuan J, Zhou J, Chen BC, Zhang X, Zhou HM, Du DF, et al. Magnesium supplementation prevents chronic cyclosporine nephrotoxicity via adjusting nitric oxide synthase activity. Transplant Proceed 2005; 37(4): 1892-5
  • 25. Eshraghi-Jazi F, Nematbakhsh M, Nasri H, Talebi A, Haghighi M, Pezeshki Z, et al. The protective role of endogenous nitric oxide donor (L-arginine) in cisplatin-induced nephrotoxicity: Gender related differences in rat model. J Res Med Sci. 2011; 16(11): 1389-96[PubMed]
  • 26. Pabla N, Dong Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int. 2008; 73(9): 994-1007[DOI][PubMed]
  • 27. Chirino YI, Pedraza-Chaverri J. Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol. 2009; 61(3): 223-42[DOI][PubMed]
  • 28. Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of Cisplatin nephrotoxicity. Toxins (Basel). 2010; 2(11): 2490-518[DOI][PubMed]
  • 29. Pan BF, Sweet DH, Pritchard JB, Chen R, Nelson JA. A transfected cell model for the renal toxin transporter, rOCT2. Toxicol Sci. 1999; 47(2): 181-6[PubMed]
  • 30. Kolb RJ, Ghazi AM, Barfuss DW. Inhibition of basolateral transport and cellular accumulation of cDDP and N-acetyl- L-cysteine-cDDP by TEA and PAH in the renal proximal tubule. Cancer Chemother Pharmacol. 2003; 51(2): 132-8[DOI][PubMed]
  • 31. Grover B, Auberger C, Sarangarajan R, Cacini W. Functional impairment of renal organic cation transport in experimental diabetes. Pharmacol Toxicol. 2002; 90(4): 181-6[PubMed]
  • 32. Ammer U, Natochin Yu, David C, Rumrich G, Ullrich KJ. Cisplatin nephrotoxicity: site of functional disturbance and correlation to loss of body weight. Ren Physiol Biochem. 1993; 16(3): 131-45[PubMed]
  • 33. Ohno T, Kato S, Wakatsuki M, Noda SE, Murakami C, Nakamura M, et al. Incidence and temporal pattern of anorexia, diarrhea, weight loss, and leukopenia in patients with cervical cancer treated with concurrent radiation therapy and weekly cisplatin: comparison with radiation therapy alone. Gynecol Oncol. 2006; 103(1): 94-9[DOI][PubMed]
  • 34. Lajer H, Kristensen M, Hansen HH, Christensen S, Jonassen T, Daugaard G. Magnesium and potassium homeostasis during cisplatin treatment. Cancer Chemother Pharmacol. 2005; 55(3): 231-6[DOI][PubMed]
  • 35. Martin M, Diaz-Rubio E, Casado A, Lopez Vega JM, Sastre J, Almenarez J. Intravenous and oral magnesium supplementations in the prophylaxis of cisplatin-induced hypomagnesemia. Results of a controlled trial. Am J Clin Oncol. 1992; 15(4): 348-51[PubMed]
  • 36. Ikarashi N, Ushiki T, Mochizuki T, Toda T, Kudo T, Baba K, et al. Effects of magnesium sulphate administration on aquaporin 3 in rat gastrointestinal tract. Biol Pharm Bull. 2011; 34(2): 238-42[PubMed]
  • 37. Song Y, He K, Levitan EB, Manson JE, Liu S. Effects of oral magnesium supplementation on glycaemic control in Type 2 diabetes: a meta-analysis of randomized double-blind controlled trials. Diabet Med. 2006; 23(10): 1050-6[DOI][PubMed]
  • 38. Lajer H, Kristensen M, Hansen HH, Nielsen S, Frokiaer J, Ostergaard LF, et al. Magnesium depletion enhances cisplatin-induced nephrotoxicity. Cancer Chemother Pharmacol. 2005; 56(5): 535-42[DOI][PubMed]
  • 39. Mavichak V, Wong NL, Quamme GA, Magil AB, Sutton RA, Dirks JH. Studies on the pathogenesis of cisplatin-induced hypomagnesemia in rats. Kidney Int. 1985; 28(6): 914-21[PubMed]
  • 40. Nielsen F, Mikkelsen BB, Nielsen JB, Andersen HR, Grandjean P. Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin Chem. 1997; 43(7): 1209-14[PubMed]
  • 41. Nagai N, Takeda A, Itanami Y, Ito Y. Co-administration of water containing magnesium ion prevents loxoprofen-induced lesions in gastric mucosa of adjuvant-induced arthritis rat. Biol Pharm Bull. 2012; 35(12): 2230-7[PubMed]
  • 42. Saleh S, El-Demerdash E. Protective effects of L-arginine against cisplatin-induced renal oxidative stress and toxicity: role of nitric oxide. Basic Clin Pharmacol Toxicol. 2005; 97(2): 91-7[DOI][PubMed]
  • 43. Wink DA, Cook JA, Christodoulou D, Krishna MC, Pacelli R, Kim S, et al. Nitric oxide and some nitric oxide donor compounds enhance the cytotoxicity of cisplatin. Nitric Oxide. 1997; 1(1): 88-94[DOI][PubMed]
  • 44. Filipski KK, Mathijssen RH, Mikkelsen TS, Schinkel AH, Sparreboom A. Contribution of organic cation transporter 2 (OCT2) to cisplatin-induced nephrotoxicity. Clin Pharmacol Ther. 2009; 86(4): 396-402[DOI][PubMed]
  • 45. Yokoo K, Murakami R, Matsuzaki T, Yoshitome K, Hamada A, Saito H. Enhanced renal accumulation of cisplatin via renal organic cation transporter deteriorates acute kidney injury in hypomagnesemic rats. Clin Exp Nephrol. 2009; 13(6): 578-84[DOI][PubMed]
Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .

Search Relations:



Create Citiation Alert
via Google Reader

Readers' Comments