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This study was done in order to investigate time-dependent effect of AFB1 on expression of genes involving in cell cycle check point machinery at G, S, and M phases. For this purpose, 24 mature male Swiss albino mice were randomly divided into control and test groups. The animals in test group subdivided into three groups, which received the AFB1 at a daily dose of 20 µg/kg body weight, through intraperitoneal (i.p.) route, for 7, 14, and 21 days. The p21, p53, cyclin D1, CDK4, and ERα expressions at both mRNA and protein level were analyzed by using reverse transcription PCR (RT-PCR) and immunohistochemistry, respectively. Moreover, the tubular differentiation (TDI) and spermiogenesis (SPI) indices were analyzed. Finally, the testicular DNA fragmentation was assessed by using DNA Ladder test. Observations revealed that the AFB1 remarkably (P < .05) reduced cyclin D1, Cdk4, and ERα expression at both mRNA and protein levels. Up-regulated p21 and p53 expression was revealed in AFB1-received animals, which developed time dependently. Histological examinations exhibited a significant reduction in TDI and SPI indices. Finally, the AFB1 resulted in severe DNA fragmentation. Our data showed that the AFB1 by down-regulating the cyclin D1, Cdk4, and ERα expression adversely affects cyclin D1/Cdk4 and cyclin D1/ERα interactions. Moreover, the AFB1-induced overexpression of p21 (as a kinase inhibitor), in turn results in cell cycle arrest via inhibiting the Cdk4 interaction with cyclin D1. Finally, the AFB1-induced DNA damage triggers the p53-dependent apoptosis pathway independent to p21 overexpression.

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Objective: Methylphenidate, Ritalin, is one of the most common medications. The administration of Ritalin leads to increase of the activity of central nervous system. Ritalin may be used for maintaining alertness and improving of attention which, may lead to increase of the risk of substance abuse in some cases. There is a little data about the effects of long term treatment with Ritalin on body organs involved in fertility ability. Regarding to the effect of normal fertility on the physical and mental health of males, this study was designed to investigate the time dependent effects of MPH on the activity of male reproductive system. Methods: Ritalin was administrated to adult rats (10 mg/kg/day) in three experimental groups for periods of two weeks, 11 weeks and 11 weeks with one week interval between each two weeks. The blood plasma levels of gonadotropins and testosterone was measured. Histomorphometrical study and sperm analysis was performed for evaluation of reproductive function. Results: The reduction in body weight and decline in the blood testosterone levels was seen in two groups which treated for 11 weeks. The reduction of microscopic indices of spermatogenesis and the alteration of morphometeric characteristics of seminiferous tubules was accompanied with epididymal sperm decrement in long term treated animals. Conclusion: The findings of this study indicate that, the long term use of methylphenidate can adversely damage the male fertility due to impairment of normal spermatogenesis. [J Exp Integr Med 2013; 3(2.000): 121-125