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Remedial effect of DL-α-lipoic acid against adriamycin induced testicular lipid peroxidation

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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 testicular toxicity. In the present study, the effect of lipoic acid, a “universal antioxidant” was investigated on ADR induced peroxidative damages in rat testis. Adult male albino rats of Wistar strain were administered ADR (1 mg/kg body weight, i.v.) once a week for 10 weeks. ADR injected rats showed a significant decline in the activities of enzymic antioxidants (catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase) and non-enzymic antioxidants (reduced glutathione, Vitamin A, Vitamin C and Vitamin E) with high malondialdehyde levels. The extent of testicular toxicity was evident from the decreased activities of testicular marker enzymes (sorbitol dehydrogenase and glucose-6-phosphate dehydrogenase). Treatment with lipoic acid (35 mg/kg body weight, i.p.) one day prior to ADR administration, maintained near normal activities of the enzymes and significantly reduced lipid peroxidation, thereby proving it to be an effective cytoprotectant. (Mol Cell Biochem 267: 209–214, 2004)

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References

  1. Lui RC, Laregina MC, Herbold DR, Johnson FE: Testicular cytotoxicity of intravenous doxorubicin in rats. J Urol 136: 940–943, 1986

    PubMed  Google Scholar 

  2. Lunenfeld B, Insler V: Infertility Male and Female. Churchill Livingstone, Edinburgh, 1993, pp 3–7

    Google Scholar 

  3. Kato M, Makino S, Kimura H, Ota T, Furuhashi T, Nagamura Y: Sperm motion analysis in rats treated with adriamycin and its applicability to male reproductive toxicity studies. J Toxicol Sci 26: 51–59, 2001

    PubMed  Google Scholar 

  4. Kang J, Lee Y, No K, Jung E, Sung J, Kim Y, Nam S: Ginseng intestinal metabolite-I (GIM-I) reduces doxorubicin toxicity in mouse testis. Reprod Toxicol 16: 291–298, 2002

    PubMed  Google Scholar 

  5. Sjoblom T, West A, Landetie J: Apoptotic response of spermatogenic cells to germ cell mutagens etopside, adriamycin and diepoxybutane. Environ Mol Mutagen 31: 133–148, 1998

    PubMed  Google Scholar 

  6. Ward JA, Bardin CW, Knight M, Robinson J, Gunsalus G, Morris ID: Delayed effect of doxorubicin on spermatogenesis and endocrine function in rats. Reprod Toxicol 2: 117–126, 1988

    PubMed  Google Scholar 

  7. Doroshow JH: Effect of anthracycline antibiotics on oxygen radical formation in rat heart. Cancer Res 43: 460–472, 1983

    PubMed  Google Scholar 

  8. Mimnaugh EG, Trush MA, Gram TE: Apossible role of membrane lipid peroxidation in anthracycline nephrotoxicity. Biochem Pharmacol 35: 4327–4335, 1986

    PubMed  Google Scholar 

  9. Sikka SC: Oxidative stress and role of antioxidants in normal and abnormal sperm function. Front Biosci 1: e78–e86, 1996

    PubMed  Google Scholar 

  10. Quiles JL, Huertas JR, Battino M, Matix J, Tortosa CR: Antioxidant nutrients and adriamycin toxicity. Toxicology 180: 79–95, 2002

    PubMed  Google Scholar 

  11. Packer L, Witt EH, Tritschler HJ: Alpha-lipoic as biological antioxidant. A Review. Free Radic Biol Med 19: 227–250, 1995

    PubMed  Google Scholar 

  12. Suzuki YJ, Tsuchiya M, Packer L: Antioxidant activities of dihydrolipoic acid and its structural homologues. Free Radic Res Commun 18: 115–122, 1993

    PubMed  Google Scholar 

  13. Kagan VE, Shvedova A, Serbinova E, Khan S, Swanson C, Powell R, Packer L: Dihydrolipoic acid — a universal antioxidant both in the membrane and in the aqueous phase. Biochem Pharmacol 44: 1637–1649, 1992

    PubMed  Google Scholar 

  14. Somani SM, Husain K, Whitworth C, Trammell GL, Malafa M, Rybak LP: Dose dependent protection by lipoic acid against cisplatin — induced nephrotoxicity in rats: Antioxidant defense system. Pharmacol Toxicol 86: 234–241, 2000

    PubMed  Google Scholar 

  15. Rudich A, Tirosh A, Potashnik R, Khamaisi M, Bashan N: Lipoic acid protects against oxidative stress induced impairment in insulin stimulation of proteinkinase B and glucose transport in 3T3-L1 adipocytes. Diabetology 42: 949–957, 1999

    Google Scholar 

  16. Greenamyre JT, Garcia-Osuna M, Greene JG: The endogenous cofactors, thioctic acid and dihydrolipoic acid, are neuroprotective against NMDA and malonic acid lesions of striatum. Neurosci Lett 171: 17–20, 1994

    PubMed  Google Scholar 

  17. Lowry OH, Rosenbrough NJ, Farr AI, Randall RJ: Protein measurement with the Folinphenol reagent. J Biol Chem 193: 265–275, 1951

    PubMed  Google Scholar 

  18. Devasagayam TPA: Lipid peroxidation in rat uterus. Biochem Biophys Acta 876: 507–514, 1986

    PubMed  Google Scholar 

  19. Sinha AK: Colorimetric assay of catalase. Annal Biochem 47: 389–394, 1972

    Google Scholar 

  20. Marklund S, Marklund G: Involvement of superoxide anion radical in the autoxidation of pyrrogallol and a covenient assay for superoxide dismutase. Eur J Biochem 47: 469–474, 1974

    PubMed  Google Scholar 

  21. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG: Selenium: Biochemical role as a component of glutathione peroxidase. Science 179: 588–590, 1973

    PubMed  Google Scholar 

  22. Staal GE, Visser J, Veeger C: Purification and properties of glutathione reductase of human erythrocytes. Biochim Biophys Acta 185: 39–48, 1969

    PubMed  Google Scholar 

  23. Habig WH, Pabst MJ, Jacob WB: Glutathione-S-transferase. The first enzymatic step in mercapturic acid formation. J Biol Chem 249: 7130–7139, 1974

    PubMed  Google Scholar 

  24. Beutler E: Active transport of glutathione disulfide from erythrocytes. In: A Larson, S Orrenius, A Holmgren, B Mannerwik (eds). Functions of Glutathione: Biochemical, Physiological, Toxicological and Clinical Aspects. Raven Press, New York, 1983, p 65

    Google Scholar 

  25. Bergmeyer HU: Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 744–761

    Google Scholar 

  26. Moron MS, Defierre JW, Mannervik B: Levels of glutathione, glutathione reductase, glutathione-S-transferase activities in rat lung and liver. Biochim Biophys Acta 582: 67–78, 1979

    PubMed  Google Scholar 

  27. Desai ID: Vitamin E analysis methods for animal tissues. Methods Enzymol 105: 138–147, 1984

    PubMed  Google Scholar 

  28. Omaye ST, Turnbull JD, Sauberlich HE: Selected methods for the determination of ascorbic acid in animal cell, tissues and fluids. Methods Enzymol 62: 3–11, 1979

    PubMed  Google Scholar 

  29. Bayfield HT, Cole EA: Colorimetric estimation of vitamin A with trichloroacetic acid. Methods Enzymol 67: 189–195, 1980

    PubMed  Google Scholar 

  30. Tsunenari I, Kawachi M, Matsumaru T, Katsuki S: Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats. Testicular toxicity of adriamycin observed 2 and 4 weeks after a single intravenous administration. J Toxicol Sci 25: 103–115, 2000

    PubMed  Google Scholar 

  31. Doroshow JT: Anthracycline antibiotic stimulated superoxide, hydrogen peroxide and hydroxul radical production by NADH dehydrogenase. Cancer Res 43: 4543–4551, 1983

    PubMed  Google Scholar 

  32. Latchoumycandane C, Mathur PP: Effect of methoxychlor on the antioxidant system in mitochondrial and microsomal rich fractions of rat testis. Toxicology 176: 67–75, 2002

    PubMed  Google Scholar 

  33. Jow WW, Schleger PN, Chichon Z, Phillips D, Goldstein M, Bardin W: Identification and localization of copper-zinc superoxide dismutase gene expression in rat testicular development. J Androl 14: 439–447, 1993

    PubMed  Google Scholar 

  34. Eklow L, Moldeus P, Orrenius S: Oxidation of glutathione during hydroperoxide metabolism. Astudy using isolated hepatocytes and the glutathione reduction inhibitor 1,3-bis (2-chloroethyl)-1-nitrosourea. Eur J Biochem 138: 459–463, 1984

    PubMed  Google Scholar 

  35. Papas AM: Antioxidant Status, Diet, Nutrition and Health. CRC Press, New York, 1998, pp 133–210

    Google Scholar 

  36. Balachandar AV, Malarkodi KP, Varalakshmi P: Protective role of DL-α-lipoic acid against adriamycin-induced cardiac lipid peroxidation. Hum Exp Toxicol 22: 249–254, 2003

    PubMed  Google Scholar 

  37. Malarkodi KP, Balachandar AV, Varalakshmi P: Protective effect of lipoic acid on adriamycin induced lipid peroxidation in rat kidney. Mol Cell Biochem 247: 9–13, 2003

    PubMed  Google Scholar 

  38. Mills NC, Means AR: Sorbitol dehydrogenase of rat testis, changes of activity during development after hypophysectomy and following gonadotrophic hormone administration. Endocrinology 91: 47–56, 1972

    Google Scholar 

  39. Prasad AK, Pant N, Srivastava SC, Kumar R, Srivastava SP: Effect of dermal application of hexachlorocyclohexane (HCH) on male reproductive system of rat. Hum Exp Toxicol 14: 484–488, 1995

    PubMed  Google Scholar 

  40. Haugaard N, Haugaard ES: Stimulation of glucose utilization by thioctic acid in rat diaphragm incubated in vitro. Biochim Biophys Acta 222: 583–586, 1970

    PubMed  Google Scholar 

  41. Pryor WA: Free radical reactions and their importance in biological systems. Fed Proc 32: 1862–1869, 1973

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  43. Sumathi R, Baskaran G, Varalakshmi P: Relationship between GSH and DL-α-lipoic acid against cadmium-induced hepatotoxicity. Jpn J Med Sci Biol 49: 39–48, 1996

    PubMed  Google Scholar 

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Prahalathan, C., Selvakumar, E. & Varalakshmi, P. Remedial effect of DL-α-lipoic acid against adriamycin induced testicular lipid peroxidation. Mol Cell Biochem 267, 209–214 (2004). https://doi.org/10.1023/B:MCBI.0000049385.13773.23

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