TY - JOUR
T1 - Protective effect of lipoic acid on cyclophosphamide-induced testicular toxicity
AU - Selvakumar, Elangovan
AU - Prahalathan, Chidambaram
AU - Sudharsan, Periyasamy Thandavan
AU - Varalakshmi, Palaninathan
N1 - Funding Information:
We acknowledge the financial assistance in the form of Senior Research Fellowship by the Indian Council of Medical Research (ICMR), New Delhi, India. We are grateful to Dr. P.R. Deepa for her valuable assistance in preparing this manuscript.
PY - 2006/5
Y1 - 2006/5
N2 - 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 γ-glutamyl transferase, β-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.
AB - 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 γ-glutamyl transferase, β-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.
KW - Cyclophosphamide
KW - Lipoic acid
KW - Marker enzymes
KW - Reactive oxygen species
KW - Testicular toxicity
KW - Thiols
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U2 - 10.1016/j.cca.2005.11.034
DO - 10.1016/j.cca.2005.11.034
M3 - Article
C2 - 16451798
AN - SCOPUS:33645831329
SN - 0009-8981
VL - 367
SP - 114
EP - 119
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
IS - 1-2
ER -