Ghoneim Fatma M, Khalaf Hanaa A, Elsamanoudy Ayman Z, Helaly Ahmed N
Department of Histology and Cell Biology, Faculty of Medicine, Mansoura University Egypt.
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University Egypt.
Int J Clin Exp Pathol. 2014 Oct 15;7(11):7323-41. eCollection 2014.
This study was designed to demonstrate the histopathological and biochemical changes in rat cerebral cortex and testicles due to chronic usage of tramadol and the effect of withdrawal. Thirty adult male rats weighing 180-200 gm were classified into three groups; group I (control group) group II (10 rats received 50 mg/kg/day of tramadol intraperitoneally for 4 weeks) and group III (10 rats received the same dose as group II then kept 4 weeks later to study the effect of withdrawal). Histological and immunohistochemical examination of cerebral cortex and testicular specimens for Bax (apoptotic marker) were carried out. Testicular specimens were examined by electron microscopy. RT-PCR after RNA extraction from both specimens was done for the genes of some antioxidant enzymes .Also, malondialdehyde (MDA) was measured colourimetrically in tissues homogenizate. The results of this study demonstrated histological changes in testicular and brain tissues in group II compared to group I with increased apoptotic index proved by increased Bax expression. Moreover in this group increased MDA level with decreased gene expression of the antioxidant enzymes revealed oxidative stress. Group III showed signs of improvement but not returned completely normal. It could be concluded that administration of tramadol have histological abnormalities on both cerebral cortex and testicular tissues associated with oxidative stress in these organs. Also, there is increased apoptosis in both organs which regresses with withdrawal. These findings may provide a possible explanation for delayed fertility and psychological changes associated with tramadol abuse.
本研究旨在证明长期使用曲马多对大鼠大脑皮质和睾丸造成的组织病理学和生化变化以及戒断效应。将30只体重180 - 200克的成年雄性大鼠分为三组；第一组（对照组），第二组（10只大鼠腹腔注射50毫克/千克/天的曲马多，持续4周），第三组（10只大鼠接受与第二组相同剂量的曲马多，4周后停药以研究戒断效应）。对大脑皮质和睾丸标本进行Bax（凋亡标志物）的组织学和免疫组织化学检查。睾丸标本通过电子显微镜检查。从两种标本中提取RNA后进行RT-PCR检测一些抗氧化酶的基因。此外，用比色法测定组织匀浆中的丙二醛（MDA）。本研究结果表明，与第一组相比，第二组的睾丸和脑组织出现组织学变化，Bax表达增加证明凋亡指数升高。此外，该组MDA水平升高，抗氧化酶基因表达降低，显示出氧化应激。第三组显示出改善迹象，但未完全恢复正常。可以得出结论，曲马多给药会使大脑皮质和睾丸组织出现组织学异常，并伴有这些器官的氧化应激。此外，两个器官的凋亡均增加，且戒断后凋亡减少。这些发现可能为与曲马多滥用相关的生育延迟和心理变化提供一种可能的解释。
