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Counteracting adriamycin-induced oxidative stress by administration of N-acetyl cysteine and vitamin E

  • Periandavan Kalaiselvi , Viswanathan Pragasam , Srinivasan Chinnikrishnan , Coothan Kandaswamy Veena , Rajaguru Sundarapandiyan and Palaninathan Varalakshmi
Published/Copyright: September 21, 2011

Abstract

Adriamycin (ADR), a cytotoxic antineoplastic drug, is used in the treatment of various solid tumors. However, its efficacy continues to be challenged by significant toxicities including nephrotoxicity. In the present study, the effects of N-acetyl cysteine (NAC) and vitamin E, known antioxidants, were investigated on ADR-induced peroxidative damage in rat kidney. Adult male albino rats of Wistar strain were administered ADR as a single dose (10mg/kg body weight, i.v.). Histopathological studies indicated that ADR-treated kidney sections show focal tubular necrosis and casts. ADR-injected rats showed a significant decline in the activities/levels of enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase) and non-enzymic antioxidants (thiols, vitamin C and vitamin E) with high malondialdehyde levels. The extent of nephrotoxicity was evident from the increased activities of urinary marker enzymes (alkaline phosphatase, lactate dehydrogenase and γ-glutamyltransferase). Treatment with NAC and vitamin E (50mg/kg b.w., i.p.) 1day prior to ADR administration maintained near normal activities of the enzymes, significantly reduced lipid peroxidation and prevented the necrosis caused by ADR, thereby proving to be an effective thiol replenishing agent and antioxidant.


Corresponding author: Dr. P. Kalaiselvi, PhD, Lecturer, Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai – 600 113, India Phone: +91-44-2492-5548, Fax: +91-44-2492-6709,

References

1. Blum RH. An overview of studies with adriamycin (NSC 123127) in the United States. Cancer Chemother Rep 1975; 6: 247–56. Search in Google Scholar

2. Singal PK, Deally CM, Weinberg LL. Sub-cellular effects of adriamycin in the heart: a concise review. J Mol Cell Cardiol 1987; 19: 817–28. 10.1016/S0022-2828(87)80392-9Search in Google Scholar

3. Homes HD, Weinberg JM. Toxic nephropathies. In: Brenner BM, Rector Jr FC, editors. Kidney. Philadelphia: Saunders, 1986:1491–533. Search in Google Scholar

4. Bertani T, Poggi A, Pozzoni R, Delaini F, Sacchi G, Thoua Y, et al. Adriamycin-induced nephritic syndrome in rats: sequence of pathologic events. Lab Invest 1982; 46: 16–21. Search in Google Scholar

5. Jovanovic D, Dimitrijevic J, Varagic J, Jovovic D, Starcevic A, Djukanovic L. Effects of captopril on morphologic changes in kidney on spontaneously hypertensive rats with adriamycin nephropathy. Ren Fail 1998; 20: 451–8. 10.3109/08860229809045134Search in Google Scholar

6. Mimnaugh EG, Trush MA, Gram TE. A possible role of membrane lipid peroxidation in anthracycline nephrotoxicity. Biochem Pharmacol 1986; 35: 4327–35. 10.1016/0006-2952(86)90713-6Search in Google Scholar

7. Bergendi L, Benes L, Durackova Z, Ferencik M. Chemistry, physiology and pathology of free radicals. Life Sci 65; 1999: 1865–74. 10.1016/S0024-3205(99)00439-7Search in Google Scholar

8. Ruffmann R, Wende A. GSH rescue by N-acetyl cysteine. Klin Wochenschr 1991; 69: 857–62. 10.1007/BF01649460Search in Google Scholar PubMed PubMed Central

9. Bernhard HL, George BC, Jerry RM. Mechanism of action of N-acetyl cysteine in the protection against the hepatotoxicity of acetaminophen in rats in vivo. J Clin Invest 1983; 71: 980–91. 10.1172/JCI110853Search in Google Scholar PubMed PubMed Central

10. Fan J, Shen SJ. The role of Tamm-Horsfall mucoprotein in calcium oxalate crystallization. N-acetyl cysteine – a new therapy for calcium oxalate urolithiasis. Br J Urol 1994; 74: 288–93. 10.1111/j.1464-410X.1994.tb16612.xSearch in Google Scholar

11. Doroshow JH, Locker GY, Ifrim I, Myers CE. Prevention of doxorubicin cardiac toxicity in the mouse by N-acetyl cysteine. J Clin Invest 1981; 68: 1053–64. 10.1172/JCI110328Search in Google Scholar PubMed PubMed Central

12. Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast agent induced reductions in renal function by acetylcholine. N Engl J Med 2000; 343: 210–2. 10.1056/NEJM200007203430304Search in Google Scholar PubMed

13. Burton GW, Traber MG. Vitamin E: antioxidant activity, biokinetics and bioavailability. Annu Rev Nutr 1990; 10: 357–63. 10.1146/annurev.nu.10.070190.002041Search in Google Scholar PubMed

14. Otani H, Mune M, Yukawa S, Smith D, Meydani M, Blumberg J. Vitamin E treatment of experimental glomerulor disease in rats. Kidney Int 1999; 56: S66–9. 10.1046/j.1523-1755.1999.07117.xSearch in Google Scholar

15. Cook MG, Mc Namara D. Effect of Vitamin E on dimethyl hydrazine induced colonic tumors in mice. Cancer Res 1980; 40: 1329–31. Search in Google Scholar

16. Marklund S, Marklund G. Involvement of superoxide anion radical in the autoxidation of pyrogallol and convenient assay for superoxide dismutase. Eur J Biochem 1974; 47: 469–74. 10.1111/j.1432-1033.1974.tb03714.xSearch in Google Scholar

17. Sinha AK. Colometric assay of catalase. Anal Biochem 1972; 47: 389–94. 10.1016/0003-2697(72)90132-7Search in Google Scholar

18. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science 1973; 179: 588–90. 10.1126/science.179.4073.588Search in Google Scholar

19. Habig WH, Pabst MJ, Jacob WB. Glutathione-S-transferase. The first enzymatic step in mercapturic and formation. J Biol Chem 1974; 249: 7310–9. Search in Google Scholar

20. Staal GE, Visser J, Veeger C. Purification and properties of glutathione reductase of human erythrocytes. Biochim Biophys Acta 1969; 185: 39–48. 10.1016/0005-2744(69)90280-0Search in Google Scholar

21. Beutler E. Active transport of glutathione disulfide from erythrocytes. In: Larson A, Orrenius S, Holmgren A, Mannerwik B, editors. Functions of glutathione biochemical, physiological, toxicological and clinical aspects. New York: Raven Press, 1983:65. Search in Google Scholar

22. Moron MS, Despierre JW, Manervik B. Levels of glutathione, glutathione reductase and glutathione-S-transferase activities in rat lung and liver. Biochim Biophys Acta 1979; 582: 67–78. 10.1016/0304-4165(79)90289-7Search in Google Scholar

23. Sedlak J, Lindsay RH. Estimation of total protein bound and non protein bound sulphydryl group in the tissue with Ellmann's reagent. Anal Biochem 1968; 25: 192–205. 10.1016/0003-2697(68)90092-4Search in Google Scholar

24. Barker H, Frank O. Clinical vitaminology methods and interpretation. New York: Interscience Publishers John Wiley and Sons, 1968:172–4. Search in Google Scholar

25. Omaye ST, Turabull JD, Sauberlich HE. Selected methods for the determination of ascorbic acid in animal cells, tissues and fluids. Methods Enzymol 1979; 62: 3–11. 10.1016/0076-6879(79)62181-XSearch in Google Scholar

26. Devasagayam TP. Lipid peroxidation in rat uterus. Biochim Biophys Acta 1986; 876: 507–14. 10.1016/0005-2760(86)90038-XSearch in Google Scholar

27. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265–75. 10.1016/S0021-9258(19)52451-6Search in Google Scholar

28. King J. The phosphohydrolases – acid and alkaline phosphatase. In: Van D, editor. Practical clinical enzymology. London: Nostrand Co. Ltd., 1965:191–208. Search in Google Scholar

29. Orlowski M, Meister A. Isolation of γ-glutamyl transpeptidase from hog kidney. J Biol Chem 1965; 240: 348–57. 10.1016/S0021-9258(18)97654-4Search in Google Scholar

30. King J. The dehydrogenase or oxidoreductases. Lactate dehydrogenase. In: Van D, editor. Practical clinical enzymology. London: Nostrand Co. Ltd., 1965:83–93. Search in Google Scholar

31. Owens JK, Iggo B, Scandretta FJ, Stewart CP. Determination of creatinine in plasma or serum and in urine: a critical examination. Biochem J 1954; 58: 426–37. 10.1042/bj0580426Search in Google Scholar

32. Bertani T, Cutillo F. Tubulo-interstitial lesions mediate renal damage in adriamycin glomerulopathy. Kidney Int 1986; 30: 488–96. 10.1038/ki.1986.212Search in Google Scholar

33. Malarkodi KP, Balachandar AV, Varalakshmi P. The influence of lipoic acid on adriamycin induced nephrotoxicity in rats. Mol Cell Biochem 2003; 247: 15–22. 10.1023/A:1024118519596Search in Google Scholar

34. Braden CV, Deman A, Ceyssens B, Pauwels M, Empsen C, Verbeelen D. Vitamin-E protects renal antioxidant enzymes and attenuates glomerulosclerosis in adriamycin treated rats. Nephron 2002; 91: 129–33. 10.1159/000057614Search in Google Scholar

35. Yildrim Z, Sogut S, Odaci E, Iraz M, Ozyurt M, Kotuk M, et al. Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats. Pharmacol Res 2003; 47: 149–56. 10.1016/S1043-6618(02)00282-7Search in Google Scholar

36. Ichikawa I, Kiyama S, Yoshioka T. Renal antioxidant enzymes: their regulation and function. Kidney Int 1994; 45: 1–9. 10.1038/ki.1994.1Search in Google Scholar

37. Pigeolet E, Corbiser P, Houbion A, Lambert D, Michiels C, Raes M, et al. Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen derived free radicals. Mech Ageing Dev 1990; 51: 283–97. 10.1016/0047-6374(90)90078-TSearch in Google Scholar

38. Singal PK, Siveski-Iliskovic N, Hill M, Thomas T, Li T. Combination therapy with probucol prevents adriamycin-induced cardiomyopathy. J Mol Cell 1995; 27: 1055–63. 10.1016/0022-2828(95)90074-8Search in Google Scholar

39. Simic T, Micmic-oka J, Sindjic M. Glutathione and enzymes associated with glutathione metabolism in adriamycin nephropathy. Srp Arch Celek Lek 1996; 124: 45–7. Search in Google Scholar

40. Malarkodi KP, Balachander AV, Sivaprasad R, Varalakshmi P. Prophylactic effect of lipoic acid against adriamycin-induced peroxidative damages in rat kidney. Ren Fail 2003; 25: 367–77. 10.1081/JDI-120021151Search in Google Scholar

41. Sandhya P, Varalakshmi P. Effect of lipoic acid administration on gentamycin-induced lipid peroxidation in rats. J Appl Toxicol 1997; 17: 405–8. 10.1002/(SICI)1099-1263(199711/12)17:6<405::AID-JAT459>3.0.CO;2-3Search in Google Scholar

42. Tappel AL. Vitamin E as the biological lipid antioxidant. Vitam Horm 1962; 20: 492–510. 10.1016/S0083-6729(08)60732-3Search in Google Scholar

43. Som S, Basu S, Mukerjee D. Ascorbic acid metabolism in diabetes mellitus. Metabolism 1981; 30: 572–7. 10.1016/0026-0495(81)90133-5Search in Google Scholar

44. Haenen GR, Vermeulin NP, Timmerman H, Bast A. Effects of thiols on lipid peroxidation in rat liver microsomes. Chem Biol Interact 1989; 71: 201–12. 10.1016/0009-2797(89)90035-5Search in Google Scholar

45. Muhammed H, Ramakrishnakurp CK. Distribution of adriamycin in tissues and subcellular fractions. Indian J Biochem Biophys 1979; 20: 349–52. Search in Google Scholar

46. Sener S, Braun JP, Rico AG, Bernard P, Burgat Sacaze V. Urine γ-glutamyl transferase in rat kidney toxicology-nephropathy by repeated injection of mercuric chloride; effects of sodium selenite. Toxicology 1979; 12: 299–305. 10.1016/0300-483X(79)90076-3Search in Google Scholar

Received: 2005-3-17
Accepted: 2005-6-17
Published Online: 2011-9-21
Published in Print: 2005-8-1

©2005 by Walter de Gruyter Berlin New York

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