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The influence of lipoic acid on adriamycin-induced hyperlipidemic nephrotoxicity in rats

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Abstract

Adriamycin widely used in the treatment of neoplastic conditions is nephrotoxic. In the present study the protective effect of lipoic acid was investigated in adriamycin-induced nephrotoxicity in adult male albino Wistar rats. Adriamycin-induced nephrotoxicity was characterized by hyperlipidemia, proteinuria, and hypoproteinemia, by decreased activities of the enzymes N-acetyl-β-D-glucosaminidase and cathepsin D, by increased lipid peroxidation and decreases in serum catalase and glutathione activities, and by increased urinary and serum urea, creatinine and urinary glycosaminoglycans. Pretreatment with lipoic acid restored the changes, indicating that lipoic acid is renoprotective in adriamycin nephrotoxicity.

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References

  1. Blum RH, Carter SK: Adriamycin: A new anticancer drug with significant clinical activity. Ann Intern Med 80: 249-259, 1974

    Google Scholar 

  2. Van Vleet JF, Ferrans VJ: Clinical and pathologic features of chronic adriamycin toxicosis in rabbits. Am J Vet Res 41: 1462-1469, 1980

    Google Scholar 

  3. O'Donnell MP, Michels L, Kasiske B, Raij L, Keane WF: Adriamycin-induced chronic protenuria: A structural and functional study. J Lab Clin Med 106: 62-67, 1985

    Google Scholar 

  4. Desassis JF, Raats CJ, Bakker MA, van den Born J, Berden JH: Anti proteinuric effect of ciclosporin A in adriamycin nephropathy in rats. Nephron 75: 336-341, 1997

    Google Scholar 

  5. Venkatesan N, Punithavathi D, Arumugam V: Curcumin prevents adriamycin nephrotoxicity in rats. Br J Pharmacol 129: 231-234, 2000

    Google Scholar 

  6. Geetha A: Effect of α-tocopherol on doxorubicin-induced changes in rat heart lysosomal enzymes. Ind J Exp Biol 31: 288-290, 1993

    Google Scholar 

  7. Okuda S, Oh Y, Tsuruda H, Onoyuma K, Fujimi S, Fujishima M: Adriamycin-induced nephropathy as a model of chronic progressive glomerular disease. Kidney Int 29: 502-510, 1986

    Google Scholar 

  8. Ito H, Miller SC, Billingham ME, Akimoto H, Torti SV, Wade R, Gahlmann R, Lyons G, Kedes L, Torti FM: Doxorubicin selectively inhibits muscle gene expression in cardiac muscle cells in vivo and in vitro. Proc Natl Acad Sci USA 87: 4275-4279, 1990

    Google Scholar 

  9. Bertani T, Cutillo F, Zoja C, Broggini M, Remuzzi G: Tubulo-interstitial lesions mediate renal damage in adriamycin glomerulopathy. Kidney Int 30: 488-496, 1986

    Google Scholar 

  10. Ichikawa I, Kiyama S, Yoshioka T: Renal antioxidant enzymes: Their regulation and function. Kidney Int 45: 1-9, 1994

    Google Scholar 

  11. Venkatesan N, Venkatesan P, Karthikeyan J, Arumugam V: Protection by taurine against adriamycin-induced proteinuria and hyperlipidemia in rats. Proc Soc Exp Biol Med 215: 158-164, 1997

    Google Scholar 

  12. Karpov LM, Dvuzhil'naia ED, Savvov VI, Phan Van Thuy: S35-lipoic acid distribution and its effect on pyruvate dehydrogenase activity in rats with Walker carcinoma. Vopr Onkol 23: 87-90, 1977

    Google Scholar 

  13. Jayanthi S, Varalakshmi P: Tissue lipids in experimental calcium oxalate lithiasis and the effect of DL α-lipoic acid. Biochem Int 26: 913-921, 1992

    Google Scholar 

  14. Sumathi R, Jayanthi S, Varalakshmi P: Impaired lipid metabolism in calcium oxalate stone forming rats and DL α-lipoic acid supplementation. Nutr Res 15: 59-70, 1995

    Google Scholar 

  15. Packer L, Witt EH, Tritschler HJ: Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med 19: 227-250, 1995

    Google Scholar 

  16. Devasagayam TP, Sundquist AR, Di Mascio P, Kaiser P, Sies H: Activity of thiols as singlet molecular oxygen quenchers. J Photochem Photobiol B 9: 105-116, 1991

    Google Scholar 

  17. Jain SK, Lim G: Lipoic acid decreases lipid peroxidation and protein glycosylation and increases (Na++K+) and Ca2+-ATPASE activities in high glucose-treated human erythrocytes. Free Radic Biol Med 29: 1122-1128, 2000

    Google Scholar 

  18. Herman EH, El-Hage A, Ferrans VJ: Protective effect of ICRF-187 on doxorubicin-induced cardiac and renal toxicity in spontaneously hypertensive (SHR) and normotensive (WKY) rats. Toxicol Appl Pharmacol 92: 42-53, 1988

    Google Scholar 

  19. Natelson S, Scort ML, Beffa C: A rapid method for the estimation of urea in biological fluids by means of the reaction between diacetylmonoxime and urea. Am J Clin Pathol 21: 275-281, 1951

    Google Scholar 

  20. Owens JK, Iggo B, Scandrette FJ, Stewart CP: Determination of creatinine in plasma or serum and in urine, a critical examination. Biochem J 58: 426-437, 1954

    Google Scholar 

  21. Lowry OH, Rosenbrough NT, Farr AI, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265-275, 1951

    Google Scholar 

  22. Whiteman P: The quantitative measurement of Alcian blue-glycosaminoglycan complexes. Biochem J 131: 343-350, 1973

    Google Scholar 

  23. Huang TI, Preminger GM, Poindexter J, Pak CY: Urinary glycosamino glycans in normal subjects and patients with stones. J Urol 139: 995-997, 1988

    Google Scholar 

  24. Maruhn D: Rapid colorimetric assay of β-galactosidase and N-acetyl-β-D-galactosaminidase in human urine. Clin Chim Acta 73: 453-461, 1976

    Google Scholar 

  25. Biber J, Stieger B, Haase W, Murer H: A high yield preparation for kidney brush border membranes: Different behaviour of lysosomal markers. Biochim Biophys Acta 647: 169-176, 1981

    Google Scholar 

  26. Jung DH: Colorimetry of serum cholesterol with the use of ferric acetate/uranyl acetate and ferrous sulfate/sulfuric acid reagent. Clin Chem 21: 1526-1530, 1975

    Google Scholar 

  27. Rice EW: Triglycerides in serum. In: P. Roderick (ed). Standard Methods in Clinical Chemistry, Vol. VI. Academic Press, New York, 1970, 215-222

    Google Scholar 

  28. Devasagayam TP: Lipid peroxidation in rat uterus. Biochim Biophys Acta 876: 507-514, 1986

    Google Scholar 

  29. Moron MS, Depierre JW, Manervik B: Levels of glutathione, glutathione reductase and glutathione-S-transferase activities in rat lung and liver. Biochim Biophys Acta 582: 67-78, 1979

    Google Scholar 

  30. Sinha AK: Colorimetric assay of catalase. Anal Biochem 47: 389-394, 1972

    Google Scholar 

  31. Bertani T, Cutillo F, Zoja C, Broggini M, Remuzzi G: Tubulo-interstitial lesions mediate renal damage in adriamycin glomerulopathy. Kidney Int 30: 488-496, 1986

    Google Scholar 

  32. Sandhya P, Mohandass S, Varalakshmi P: Role of DL-α-lipoic acid in gentamicin induced nephrotoxicity. Mol Cell Biochem 145: 11-17, 1995

    Google Scholar 

  33. Mettler FP, Young DM, Ward JM: Adriamycin-induced cardiotoxicity (cardiomyopathy and congestive heart failure) in rats. Cancer Res 37: 2705-2713, 1977

    Google Scholar 

  34. Raab WP: Diagnostic value of urinary enzyme determinations. Clin Chem 18: 5-25, 1972

    Google Scholar 

  35. Bertani T, Poggi A, Pozzoni R, Delaini F, Sacchi G, Thoua Y, Mecca G, Remuzzi G, Donati MB: Adriamycin-induced nephrotic syndrome in rats: Sequence of pathologic events. Lab Invest 46: 16-23, 1982

    Google Scholar 

  36. Valtin H: In: Renal Function: Mechanism Preserving Fluid and Solute Balance in Health, 2nd edn. Little Brown, Boston/Toronto, 1983

    Google Scholar 

  37. Benjelloun AS, Merville P, Cambar J, Aparicio M: Effects of a low-protein diet on urinary glycosaminoglycan excretion in adriamycintreated rats. Nephron 64: 242-248, 1993

    Google Scholar 

  38. Raats CJ, Bakker MA, van den Born J, Berden JH: Hydroxyl radicals depolymerize glomerular heparan sulfate in vitro and in experimental nephrotic syndrome. J Biol Chem 272: 26734-26741, 1997

    Google Scholar 

  39. Zima T, Tesar V, Rychlik I, Nemecek K, Poledne R, Teminova J, Slepek S, Merta M: The influence of pefloxacine on experimental adriamycin-induced nephrotic syndrome in rats. Renal Failure 18: 195-199, 1996.

    Google Scholar 

  40. Jovanovic D, Dimitrijevic J, Varagic J, Jovovic D, Starcevic A, Djukanovic L: Effects of captopril on morphological changes in kidney of spontaneously hypertensive rats with adriamycin nephropathy. Renal Failure 20: 451-458, 1998

    Google Scholar 

  41. Whiting PH, Brown PA: The relationship between enzymuria and kidney enzyme activities in experimental gentamicin nephrotoxicity. Renal Failure 18: 899-909, 1996

    Google Scholar 

  42. Singal PK, Segstro RJ, Sing RP, Kutryk MJ: Changes in lysosomal morphology and enzyme activities during the development of adriamycin-induced cardiomyopathy. Can J Cardiol 1: 139-147, 1985

    Google Scholar 

  43. Takahashi T, Schmidt PG, Tang J: Oligosaccharide units of lysosomal cathepsin D from porcine spleen: Amino acid sequence and carbohydrate structure of the glycoprotein. J Biol Chem 258: 2819-2830, 1983

    Google Scholar 

  44. Cooper B, Creeth JM, Donald AS: Studies of the limited degradation of mucous glycoproteins: The mechanism of the peroxide reaction. Biochem J 228: 615-626, 1985

    Google Scholar 

  45. Kim K, Rhee SG, Stadtman ER: Non-enzymatic cleavage of proteins by reactive oxygen species generated by dithiothreitol and iron. J Biol Chem 260: 15394-15397, 1985

    Google Scholar 

  46. Montilla P, Tunez I, Munoz MC, Lopez A, Soria JV: Hyperlipidemic nephropathy induced by adriamycin: Effect of melatonin administration. Nephron 76: 345-350, 1997

    Google Scholar 

  47. Badary OA, Abdel-Naim AB, Abdel-Wahab MH, Hamada FM: The influence of thymoquinone on doxorubicin-induced hyperlipidemic nephropathy in rats. Toxicology 143: 219-226, 2000

    Google Scholar 

  48. Weening JJ, Rennke HG: Glomerular permeability and polyanion adriamycin nephrosis in the rat. Kidney Int 24: 152-159, 1983

    Google Scholar 

  49. Wu SH, Yang YC, Wang ZM: Role of oxygen radicals in adriamycin-induced nephrosis. Chin Med J (Engl) 103: 283-289, 1990

    Google Scholar 

  50. Ginevri F, Gusmano R, Oleggini R, Acerbo S, Bertelli R, Perfumo F, Cercignani G, Allegrini S, D'Allegri F, Ghiggeri G: Renal purine efflux and xanthine oxidase activity during experimental nephrosis in rats: Difference between puromycin aminonucleoside and adriamycin nephrosis. Clin Sci (Lond) 78: 283-293, 1990

    Google Scholar 

  51. Schreck R, Baeuerle PA: A role for oxygen radicals as second messengers. Trends Cell Biol 1: 39-42, 1991

    Google Scholar 

  52. Hutchison FN: Proteinuria, hyperlipidemia, and the kidney. Miner Electrolyte Metab 19: 127-136, 1993

    Google Scholar 

  53. Soose M, Haberstroh U, Rovira-Halbach G, Brunkhorst R, Stolte H: Heterogeneity of glomerular barrier function in early adriamycin nephrosis of MWF rats. Clin Physiol Biochem 6: 310-315, 1988

    Google Scholar 

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Authors and Affiliations

  1. Department of Medical Biochemistry, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Camus, Chennai, 600 113, India

    Kumaravel Palanichamy Malarkodi, Andithangal Venkatesan Balachandar & Palaninathan Varalakshmi

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  1. Kumaravel Palanichamy Malarkodi
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  2. Andithangal Venkatesan Balachandar
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  3. Palaninathan Varalakshmi
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Malarkodi, K.P., Balachandar, A.V. & Varalakshmi, P. The influence of lipoic acid on adriamycin-induced hyperlipidemic nephrotoxicity in rats. Mol Cell Biochem 247, 139–145 (2003). https://doi.org/10.1023/A:1024175325850

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