Lipoic acid modulates adriamycin-induced testicular toxicity

被引:41
作者
Prahalathan, C [1 ]
Selvakumar, E [1 ]
Varalakshmi, P [1 ]
机构
[1] Univ Madras, Post Grad Inst Bas Med Sci, Dept Med Biochem, Madras 600113, Tamil Nadu, India
关键词
adriamycin; lipoic acid; 8-hydroxy-2-deoxyguanosine; DNA damage; steroidogenic enzymes; flow cytometry; testicular toxicity;
D O I
10.1016/j.reprotox.2005.07.002
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Adriamycin (ADR), an anthracycline antibiotic, which is widely used as an antineoplastic drug in the treatment of various solid tumors, has been shown to induce reproductive abnormalities in males. In the present study, the effect of lipoic acid (LA) a universal antioxidant was investigated on ADR-induced testicular toxicity in rats. 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 increased levels of 8-hydroxy-2-deoxyguanosine with high protein carbonyl contents in testicular tissue. These changes were associated with significant increase in DNA damage in the sperm as evidenced by increased single strand breaks in a fluorimetric analysis of DNA unwinding (FADU). The activities of steroidogenic enzymes such as 30-hydroxy steroid dehydrogenase and 17 beta-hydroxy steroid dehydrogenase, serum testosterone levels were decreased significantly in ADR-treated rats. Flow cytometric evaluation of testicular tissue in ADR-administered rats revealed impaired spermatogenesis and testicular function. Treatment with lipoic acid (35 mg/kg body weight, i.p.) one day prior to ADR administration, maintained near normal steroidogenesis and spermatoenesis, thereby proving it to be an effective cytoprotectant. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:54 / 59
页数:6
相关论文
共 29 条
[1]   Ultrasensitive and specific detection methods for exocylic DNA adducts: Markers for lipid peroxidation and oxidative stress [J].
Bartsch, H ;
Nair, J .
TOXICOLOGY, 2000, 153 (1-3) :105-114
[2]  
BERGMEYER HU, 1974, METHOD ENZYMAT AN, V1, P476
[3]  
BIRNBOIM HC, 1990, METHOD ENZYMOL, V186, P550
[4]   Reactive oxygen disrupts mitochondria in MA-10 tumor Leydig cells and inhibits steroidogenic acute regulatory (StAR) protein and steroidogenesis [J].
Diemer, T ;
Allen, JA ;
Hales, KH ;
Hales, DB .
ENDOCRINOLOGY, 2003, 144 (07) :2882-2891
[5]   COMPARISON OF HISTOLOGIC AND FLOW CYTOMETRIC EVALUATION OF CYCLOPHOSPHAMIDE-INDUCED TESTICULAR DAMAGE [J].
GOLDBERG, SD ;
DEITCH, AD ;
SCHEVCHUCK, M ;
NAGLER, HM ;
WHITE, RD .
UROLOGY, 1984, 24 (05) :472-475
[6]   ISOLATION OF HIGH-MOLECULAR-WEIGHT DNA FROM MAMMALIAN-CELLS [J].
GROSS-BELLARD, MM ;
OUDET, P ;
CHAMBON, P .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1973, 36 (01) :32-38
[7]   EFFECT OF ANTIOXIDANTS ON ADRIAMYCIN-INDUCED MICROSOMAL LIPID-PEROXIDATION [J].
HIDA, H ;
COUDRAY, C ;
CALOP, J ;
FAVIER, A .
BIOLOGICAL TRACE ELEMENT RESEARCH, 1995, 47 (1-3) :111-116
[8]  
ITO K, 1993, J BIOL CHEM, V268, P13221
[9]   DIHYDROLIPOIC ACID - A UNIVERSAL ANTIOXIDANT BOTH IN THE MEMBRANE AND IN THE AQUEOUS PHASE - REDUCTION OF PEROXYL, ASCORBYL AND CHROMANOXYL RADICALS [J].
KAGAN, VE ;
SHVEDOVA, A ;
SERBINOVA, E ;
KHAN, S ;
SWANSON, C ;
POWELL, R ;
PACKER, L .
BIOCHEMICAL PHARMACOLOGY, 1992, 44 (08) :1637-1649
[10]   Ginseng intestinal metabolite-I (GIM-I) reduces doxorubicin toxicity in the mouse testis [J].
Kang, JK ;
Lee, YJ ;
No, KO ;
Jung, EY ;
Sung, JH ;
Kim, YB ;
Nam, SY .
REPRODUCTIVE TOXICOLOGY, 2002, 16 (03) :291-298