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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Lui RC, Laregina MC, Herbold DR, Johnson FE: Testicular cytotoxicity of intravenous doxorubicin in rats. J Urol 136: 940–943, 1986
Lunenfeld B, Insler V: Infertility Male and Female. Churchill Livingstone, Edinburgh, 1993, pp 3–7
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
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
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
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
Doroshow JH: Effect of anthracycline antibiotics on oxygen radical formation in rat heart. Cancer Res 43: 460–472, 1983
Mimnaugh EG, Trush MA, Gram TE: Apossible role of membrane lipid peroxidation in anthracycline nephrotoxicity. Biochem Pharmacol 35: 4327–4335, 1986
Sikka SC: Oxidative stress and role of antioxidants in normal and abnormal sperm function. Front Biosci 1: e78–e86, 1996
Quiles JL, Huertas JR, Battino M, Matix J, Tortosa CR: Antioxidant nutrients and adriamycin toxicity. Toxicology 180: 79–95, 2002
Packer L, Witt EH, Tritschler HJ: Alpha-lipoic as biological antioxidant. A Review. Free Radic Biol Med 19: 227–250, 1995
Suzuki YJ, Tsuchiya M, Packer L: Antioxidant activities of dihydrolipoic acid and its structural homologues. Free Radic Res Commun 18: 115–122, 1993
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
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
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
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
Lowry OH, Rosenbrough NJ, Farr AI, Randall RJ: Protein measurement with the Folinphenol reagent. J Biol Chem 193: 265–275, 1951
Devasagayam TPA: Lipid peroxidation in rat uterus. Biochem Biophys Acta 876: 507–514, 1986
Sinha AK: Colorimetric assay of catalase. Annal Biochem 47: 389–394, 1972
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
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
Staal GE, Visser J, Veeger C: Purification and properties of glutathione reductase of human erythrocytes. Biochim Biophys Acta 185: 39–48, 1969
Habig WH, Pabst MJ, Jacob WB: Glutathione-S-transferase. The first enzymatic step in mercapturic acid formation. J Biol Chem 249: 7130–7139, 1974
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
Bergmeyer HU: Methods of Enzymatic Analysis. Academic Press, New York, 1974, pp 744–761
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
Desai ID: Vitamin E analysis methods for animal tissues. Methods Enzymol 105: 138–147, 1984
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
Bayfield HT, Cole EA: Colorimetric estimation of vitamin A with trichloroacetic acid. Methods Enzymol 67: 189–195, 1980
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
Doroshow JT: Anthracycline antibiotic stimulated superoxide, hydrogen peroxide and hydroxul radical production by NADH dehydrogenase. Cancer Res 43: 4543–4551, 1983
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
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
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
Papas AM: Antioxidant Status, Diet, Nutrition and Health. CRC Press, New York, 1998, pp 133–210
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
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
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
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
Haugaard N, Haugaard ES: Stimulation of glucose utilization by thioctic acid in rat diaphragm incubated in vitro. Biochim Biophys Acta 222: 583–586, 1970
Pryor WA: Free radical reactions and their importance in biological systems. Fed Proc 32: 1862–1869, 1973
Sandhya P, Mohandass S, Varalakshmi P: Role of DL-α-lipoic acid in gentamicin induced nephrotoxicity. Mol Cell Biochem 145: 11–17, 1995
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
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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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DOI: https://doi.org/10.1023/B:MCBI.0000049385.13773.23