Methylphenidate has dose-dependent negative effects on rat spermatogenesis: Decreased round spermatids and testicular weight and increased p53 expression and apoptosis
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Date
2011
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Abstract
In the present study, we aimed to evaluate the possible effects of methylphenidate on rat testes. Forty-two Wistar rats were randomly distributed into three experimental groups of 14 rats each. For 90 days, each group via gavage received the following: group 1 = tap water (control group), group 2 = 5 mg/kg/day of ritalin (methylphenidate, MPH), and group 3 = 10 mg/kg/day of ritalin. After sacrificing the animals, the body weights as well as the absolute and relative testicular weights were measured. Testes were sampled, fixed, and processed and, by histopathological examination, quantitative morphometric analysis of Sertoli cells, spermatocytes, and spermatids was performed in stages II, V, and XII. Immunohistochemistry was performed for transforming growth factor (TGF)-β1 and p 53, and the apoptotic index was assessed through the TUNEL method. Group 2 had a reduction of round spermatids in stage II. Group 3 had reduction in both stage II and stage V spermatids, as well as lower testicular weight. The p 53 expression was increased in group 3. In groups 2 and 3, the TGF-β1 expression was reduced and the apoptotic index by TUNEL was increased. Body weights remained stable on either group. Our results showed that methylphenidate might negatively affect spermatogenesis not only by reducing testicular weight and amount of round spermatids but also by increasing apoptotic death and p 53 activation. The findings of the study, however, must be cautiously interpreted. © SAGE Publications 2011.
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Animals , Apoptosis , Body Weight , Central Nervous System Stimulants , Dopamine Uptake Inhibitors , Male , Methylphenidate , Organ Size , Rats , Rats, Wistar , Spermatogenesis , Spermatozoa , Testis , Transforming Growth Factor beta1 , Tumor Suppressor Protein p53 , Animalia , Rattus , Rattus norvegicus , methylphenidate , protein p53 , tap water , transforming growth factor beta1 , animal cell , animal experiment , apoptosis , article , body weight , cell cycle , controlled study , drug megadose , histopathologic skin reaction , immunohistochemistry , low drug dose , male , nick end labeling , nonhuman , priority journal , protein expression , rat , Sertoli cell , spermatid , spermatocyte , spermatogenesis , testis weight , Wistar rat