BACKGROUND Reported tramadol toxicity emphasizes the necessity to recognize its mechanism of toxicity, particularly to the brain tissue. AIM This study aimed to evaluate the protective effect of vitamin C (Vit C) in cerebrocortical toxicity mediated by tramadol in rats using biochemical and histological parameters. MATERIAL AND METHODS Forty-eight albino rats were randomly divided into eight groups, (n = 6/group) as follow: the control group received normal saline and vitamin C group received vitamin C (200 mg/kg per oral). Tramadol 50, 100, 150 groups received tramadol in doses of (50, 100 and 150 mg/kg per oral, respectively); Tramadol 50+ Vit C, 100+ Vit C, 150+ Vit C groups received vitamin C (200 mg/kg per oral) plus tramadol in doses of (50, 100 and 150 mg/kg per oral, respectively). Rats had received vitamin C and tramadol daily for 30 days. Blood and brain tissues samples were harvested for biochemical, histopathological, immunohistochemical and electron microscopic examinations. RESULTS Tramadol administration leads to a significant elevation of MDA, NO levels and a significant decrease in antioxidants parameters (CAT, SOD and GSH) in the tissues of cerebral cortices in rats which were directly proportional to the dose of tramadol. In histological investigations, tramadol-treated groups showed pyknotic pyramidal cells, multiple red neurons and shrinking red neurons with hallows around it and apoptotic cells were detected. These biochemical abnormalities and histological impairment were ameliorated in groups with tramadol low doses by the co-treatment with vitamin C. CONCLUSION vitamin C has antioxidant and anti-apoptotic potentials against tramadol neurotoxicity via suppression of oxidative stress, lipid peroxidation, structural abnormalities, and down-regulation of p53 and overexpression of Bcl2 in the nervous tissues.

中文翻译：

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评估维生素 C 对大鼠脑皮质抗氧化防御、组织病理学、促凋亡 p53 和抗凋亡 Bcl2 表达对曲马多神经毒性的保护作用

背景报道的曲马多毒性强调了认识其毒性机制的必要性，尤其是对脑组织的毒性。目的 本研究旨在使用生化和组织学参数评估维生素 C (Vit C) 对曲马多介导的大鼠脑皮质毒性的保护作用。材料与方法白化大鼠48只，随机分为8组，每组6只：对照组给予生理盐水，维生素C组给予维生素C（200mg/kg/组）。曲马多 50、100、150 组接受剂量为（分别为每次口服 50、100 和 150 mg/kg）的曲马多；Tramadol 50+ Vit C、100+ Vit C、150+ Vit C 组接受维生素 C（每次口服 200 mg/kg）和剂量为（分别为每次口服 50、100 和 150 mg/kg）的曲马多。大鼠每天接受维生素 C 和曲马多 30 天。收集血液和脑组织样本用于生化、组织病理学、免疫组织化学和电子显微镜检查。结果 曲马多给药导致大鼠大脑皮质组织中 MDA、NO 水平显着升高和抗氧化剂参数（CAT、SOD 和 GSH）显着降低，这与曲马多的剂量成正比。在组织学研究中，曲马多处理组显示锥体细胞固缩，多个红色神经元和收缩的红色神经元，周围有空心，并检测到凋亡细胞。这些生化异常和组织学损伤在低剂量曲马多组中通过与维生素 C 联合治疗得到改善。