Alterations in Rat’s Testicular Structure and Function following Simultaneous Administration of Nicotine and Methylphenidate: An in Vitro Dose-Response Study

Abstract

Methylphenidate (MPH) and nicotine (NCT) have deleterious effects on testicular tissue, individually. Methylphenidate intake could increase the tendency to use NCT. In this study, the possible synergistic effects of MPH and NCTon the intensity of structural and functional changes of testicular tissue were evaluated using experimental animal study. Eighty male mature Wistar rats were used. MPH (5 and 10 mg/kg, IP) and NCT (2 and 4 mg/kg, IP) were administrated individually (MPH or NCT) or simultaneously (MPH + NCT) to eight treated groups of adult rats (n = 10/group) once a day for eight weeks. After the recording of body and testicular weight, the plasma level of pituitary gonadotropins, testosterone, and malondialdehyde (MDA) as lipid peroxidation index were measured. Also, testes samples were prepared for tissue lipid peroxidation assay, histomorphology, immunohistochemistry of p53 protein, and electron microscopy. Moreover, sperm analysis was performed on cauda epididymis. There was not any significant difference in initial and final body weight between groups. Testicular weight and testicular to body weight ratio were reduced in treated groups. LH, Testosterone, and plasma and tissue MDA were increased and FSH decreased dose-dependently in the most treated groups. Most of the histomorphometric, cell population, and sperm analysis parameters were decreased in treated groups in a dose-dependent manner. The light and electron micrographs showed various alterations in testicular tissue which were more obvious in higher doses of NCT or MPH and NCT + MPH groups. Immunostaining of testicular tissue revealed upregulation of p53 in treated groups, particularly in NCT + MPH groups. The results of this study showed that simultaneous administration of NCT and MPH could induce more alterations in the structure and function of testicular tissue compared to their individual administration.

Keywords

• methylphenidate
• nicotine
• testicular tissue
• p53
• oxidative stress