Protective effect of lipoic acid on cyclophosphamide-induced testicular toxicity.
BACKGROUND
Cyclophosphamide (CP), a widely used anticancer and immunosuppressive drug causes severe testicular toxicity. We investigated the protective effect of lipoic acid in CP-induced testicular toxicity.


METHODS
Two groups of male Wistar rats (140+/-20 g) were administered CP (15 mg/kg body weight, oral gavage) once a week for 10 weeks to induce testicular toxicity; one of these groups received lipoic acid treatment (35 mg/kg body weight, i.p., 24 h prior to CP administration) once a week for 10 weeks. A vehicle treated control and a lipoic acid control groups were also included.


RESULTS
The untreated CP exposed rats showed a significant increase in testicular reactive oxygen species (ROS) level, along with a significant decrease in cellular thiol levels. The activities of testicular marker enzymes such as gamma-glutamyl transferase, beta-glucuronidase, acid phosphatase and alkaline phosphatase were increased whereas the activities of sorbitol dehydrogenase and lactate dehydrogenase-X were decreased significantly in the animals treated with CP. In contrast, rats pretreated with lipoic acid showed normal marker enzymic patterns and normal levels of ROS and thiols. Testicular protection by lipoic acid is further substantiated by the normal histologic findings as against shrunken seminiferous tubules with impaired spermatogenesis in the CP administered rats.


CONCLUSIONS
By the reversal of biochemical and morphological changes towards normalcy, the cytoprotective role of lipoic acid is illuminated in CP-induced testicular toxicity.
Selvakumar
Elangovan
E
Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, India.
Prahalathan
Chidambaram
C
Sudharsan
Periyasamy Thandavan
PT
Varalakshmi
Palaninathan
P
D000818:Animals; D015415:Biomarkers; D003520:Cyclophosphamide / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008063:Thioctic Acid / Q000494:pharmacology*
D015415:Biomarkers; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D008063:Thioctic Acid; D003520:Cyclophosphamide