Protective role of alpha-tocopherol-succinate (provitamin-E) in cyclophosphamide induced testicular gametogenic and steroidogenic disorders: a correlative approach to oxidative stress.
The present study was undertaken to find out the adverse effects of cyclophosphamide on testicular activities along with testicular oxidative stress at its therapeutic dose and the protective effects of alpha-tocopherol succinate on testicular dysfunctions induced by cyclophosphamide in mature albino rats. A significant diminution in the activities of testicular delta 5, 3 beta-hydroxysteroid dehydrogenase (HSD) and 17 beta-hydroxysteroid dehydrogenase (HSD) along with significant reduction in the plasma level of testosterone and number of spermatogonia-A (ASg), preleptotene spermatocytes (pLSc), midpachytene spermatocytes (mPSc) and step 7 spermatids (7Sd) at stage VII of spermatogenic cycle were observed following cyclophosphamide treatment. Oxidative stress was also noted in testis, which was enlightened by significant elevation in the level of malondialdehyde (MDA) and conjugated dienes along with significant reduction in the activities of testicular peroxidase and catalase. Co-administration of alpha-tocopherol succinate in cyclophosphamide-treated rats resulted a significant restoration of all the above-mentioned parameters to the control level. The results of our experiment suggest that cyclophosphamide treatment at its clinical dose is associated with antigonadal activities as well as induction of oxidative stress in gonad that can be ameliorated significantly by alpha-tocopherol succinate co-administration. So, our data have some potential clinical implications.
Ghosh
Debidas
D
Reproductive Endocrinology and Family Welfare Research Unit, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore 721102, West Bengal, India. debidasghosh@yahoo.com
Das
Ujjal Baran
UB
Misro
Manomohan
M
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D003520:Cyclophosphamide / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011375:Progesterone Reductase / Q000378:metabolism; D020011:Protective Agents / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013087:Spermatids / Q000378:metabolism; D013090:Spermatocytes / Q000378:metabolism; D013733:Testicular Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D024502:alpha-Tocopherol / Q000378:metabolism
D018906:Antineoplastic Agents, Alkylating; D000975:Antioxidants; D020011:Protective Agents; D014810:Vitamin E; D013739:Testosterone; D008315:Malondialdehyde; D003520:Cyclophosphamide; D015067:17-Hydroxysteroid Dehydrogenases; D011375:Progesterone Reductase; D002374:Catalase; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; D024505:Tocopherols