Protective Role of α-tocopherol-succinate (Provitamin-E) in Cyclophosphamide Induced Testicular Gametogenic and Steroidogenic Disorders: A Correlative Approach to Oxidative Stress

Abstract

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.

Melatonin Ratlarda Alloxan İle İndüklenen Diyabet Sonrası Oluşan Testiküler Hasarı ve Oksidatif Etkileri Hafifletir

“…In our study, the lower sperm concentration and the lower number of motile sperm in the DM group are consistent with the reproductive disorders [45,46] . Present findings with decreased sperm concentration in diabetic rats were similar to those of Bal et al [4] , while being slightly lower than those of Navarro-Casado et al…”

“…Singh et al [40] reported that the decrease in sperm density may be related to the decrease in the number of Leydig cells [4] . Some authors reported that the reduced epididymal and motile sperm concentrations in diabetic rats could arise from a combined effect of decreased Leydig cell function and the oxidative stress induced by diabetes [4,46,48,49] . It has been shown that the destructive effect of free oxygen radicals reduces the sperm motility and viability [49] .…”

Histological and immunohistochemical study of cyclophosphamide effect on adult rat testis

“…Ghosh et al stated that the difference in the testosterone level between cyclophosphamide-treated and control animals served as evidence for the damage of the testes. 7 Also, these data were strengthen the idea about the inhibitory effect of cyclophosphamide on testicular steroidogenesis and spermatogenic disorder indicated by diminution in the number of different generation of germ cells.…”

“…Moreover, the oxidative damage to this poly-unsaturated fatty acid of the cell membrane results in impairment of membrane fluidity and permeability. 7 As other chemotherapeutic drugs, cyclophosphamide has variable hazards that either persist or relief spontaneously. Few literatures were done upon the effect of cyclophosphamide on the male and female gonads and how long it persists.…”

Effects of Resistance Exercise Training on Antioxidant Enzyme and GLUT 8 Expression in Testes of Type 2 Diabetic Rats

“…Vitamin E has also been shown to suppress lipid peroxidation in testicular microsomes and mitochondria 36,37 and to reverse the detrimental effects of oxidative stress on testicular function mediated by exposure to such factors as ozone, iron overload, intensive exercise or exposure to aflatoxin, PCB, cyclophosphamide and formaldehyde. 28,32,33,[38][39][40][41][42] Furthermore testicular vitamin E levels have also been shown to fall significantly when oxidative stress is induced by exposure to pro-oxidant stimuli such as chromium. 34 Although catalase is of limited importance in the testes, there are several isoforms of GPx in this tissue that use glutathione (GSH) as a source of electrons to reduce H 2 O 2 to water.…”