Lipoic acid modulates adriamycin-induced testicular toxicity.
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 (1mg/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 3beta-hydroxy steroid dehydrogenase and 17beta-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 spermatogenesis, thereby proving it to be an effective cytoprotectant.
Prahalathan
Chidambaram
C
Department of Medical Biochemistry, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, Tamilnadu, India.
Selvakumar
Elangovan
E
Varalakshmi
Palaninathan
P
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism; D008297:Male; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D008063:Thioctic Acid / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D013739:Testosterone; D008063:Thioctic Acid; D004317:Doxorubicin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D003849:Deoxyguanosine