Human Anatomy and Embryology Department, Faculty of Medicine, Suez Canal University, Ismailia, 41522, Egypt.
Forensic Medicine and Clinical Toxicology, College of Medicine, Jouf University, Sakaka, 42421, Saudi Arabia; Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Suez Canal University, Ismailia, 41522, Egypt.
J Chem Neuroanat. 2021 Mar;112:101893. doi: 10.1016/j.jchemneu.2020.101893. Epub 2020 Dec 1.
Reported tramadol toxicity emphasizes the necessity to recognize its mechanism of toxicity, particularly to the brain tissue.
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.
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.
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.
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.
已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机制。
本研究旨在通过生化和组织学参数评估维生素 C（Vit C）对曲马多诱导的大鼠皮质毒性的保护作用。
48 只白化大鼠随机分为 8 组（每组 n=6）：对照组给予生理盐水，维生素 C 组给予维生素 C（口服 200mg/kg）。曲马多 50、100、150 组分别给予（口服 50、100 和 150mg/kg）曲马多；曲马多 50+Vit C、100+Vit C、150+Vit C 组分别给予维生素 C（口服 200mg/kg）加（口服 50、100 和 150mg/kg）曲马多。大鼠每日给予维生素 C 和曲马多，连续 30 天。采集血液和脑组织样本进行生化、组织病理学、免疫组织化学和电子显微镜检查。
曲马多给药导致大鼠皮质组织中 MDA、NO 水平显著升高，抗氧化参数（CAT、SOD 和 GSH）显著降低，且与曲马多剂量直接相关。组织学研究显示，曲马多治疗组的锥体细胞出现固缩，出现多个红色神经元和缩小的红色神经元，周围有空腔，还检测到凋亡细胞。这些生化异常和组织学损伤在低剂量曲马多联合维生素 C 治疗组中得到改善。
维生素 C 通过抑制氧化应激、脂质过氧化、结构异常，下调神经组织中 p53 和上调 Bcl2，具有对抗曲马多神经毒性的抗氧化和抗凋亡作用。
