Document Detail

Chemoprotective effect of lipoic acid against cyclophosphamide-induced changes in the rat sperm.
MedLine Citation:
PMID:  16207511     Owner:  NLM     Status:  MEDLINE    
Treatment with cyclophosphamide (CP), a commonly used anticancer and immunosuppressive agent, may result in oligospermia and azoospermia. CP administration induces oxidative stress and is cytotoxic to normal cells. In this context, we have studied the effect of an established antioxidant, lipoic acid on its influence on CP-induced oxidative injury in rat sperm. In this study, we have assessed the possible protective efficacy of lipoic acid on the sperm characteristics, peroxidative damages and abnormal antioxidant levels in the epididymal sperm of CP-administered rats. Male Wistar rats of 140+/-20 g were categorized into four groups. Two groups of rats were administered CP (15 mg/kg body weight once a week for 10 weeks by oral gavage) to induce testicular toxicity; one of these groups received lipoic acid treatment (35 mg/kg body weight intraperitoneally once a week for 10 weeks; 24 h prior to CP administration). A vehicle treated control group and a lipoic acid drug control group were also included. CP-treated rats showed a significant decrease in sperm count and motility with an increase in dead and abnormal sperms. The epididymal sperm of untreated CP-exposed rats showed 1.9-fold increase in lipid peroxidation, along with a significant increase in protein carbonyl level. These changes were associated with significant increase in DNA damage in the sperm as evidenced by increased single strand breaks in fluorimetric analysis of DNA unwinding (FADU). In rats treated with CP, abnormal changes in the activities/levels of enzymic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymic (reduced glutathione, ascorbate and alpha-tocopherol) antioxidants, were also observed. Pretreatment with lipoic acid improved the semen quality and reduced the oxidative stress and DNA damage induced by CP, thereby demonstrating the protection rendered by lipoic acid.
Elangovan Selvakumar; Chidambaram Prahalathan; Periyasamy Thandavan Sudharsan; Palaninathan Varalakshmi
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-10-03
Journal Detail:
Title:  Toxicology     Volume:  217     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-12     Completed Date:  2006-03-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  71-8     Citation Subset:  IM    
Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, Tamil Nadu, India.
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MeSH Terms
Antineoplastic Agents, Alkylating / toxicity
Ascorbic Acid / metabolism
Cyclophosphamide / toxicity*
DNA Damage / drug effects
Epididymis / drug effects,  metabolism,  pathology
Injections, Intraperitoneal
Lipid Peroxidation / drug effects
Peroxidases / antagonists & inhibitors,  metabolism
Protective Agents / administration & dosage,  pharmacology*
Protein Carbonylation / drug effects
Rats, Wistar
Sperm Count
Sperm Motility / drug effects
Spermatozoa / drug effects*,  metabolism,  pathology
Thioctic Acid / administration & dosage,  pharmacology*
Vitamin E / metabolism
Reg. No./Substance:
0/Antineoplastic Agents, Alkylating; 0/Protective Agents; 1406-18-4/Vitamin E; 50-18-0/Cyclophosphamide; 50-81-7/Ascorbic Acid; 62-46-4/Thioctic Acid; EC 1.11.1.-/Peroxidases

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