The current study was performed to study the tramadol HCL toxic effects on the brain, liver, and kidney of adult male rats. Forty male adult albino rats were divided into 4 groups; the first one was considered as a control group, the others were orally administrated with 25, 50, and 100 b.wt. representing therapeutic, double therapeutic, and 4 times therapeutic doses, respectively, of tramadol HCL daily for 1 month. Serum and brain, hepatic, and renal tissues were collected for biochemical and molecular investigations. Tramadol HCL resulted in a significant increase in the brain serotonin, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malonyldialdehyde (MDA) levels with a significant decrease in the reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. At the same line, hepatic and renal 8-OHdG and MDA levels showed a significant increase with a significant decrease in reduced glutathione (GSH), CAT, and SOD activities. In addition, hepatic and renal function parameters including serum alanine amino transferase (ALT), aspartate amino transferase (AST), urea, and creatinine were increased in a dose-dependent manner. At the molecular levels, hepatic cytochrome P5402E1 (CYP2E1), renal Kidney Injury Molecule-1 (KIM-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) showed also a significant increase in the expression levels. Histopathological evaluation of the brain confirmed the above biochemical results. In conclusion, tramadol HCL induced neurotoxic, hepatotoxic, and nephrotoxic effects in a manner relative to its concentration by affecting brain serotonin levels and hepatic and renal function, with the production of DNA damage and oxidative stress.

中文翻译：

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曲马多给药对大鼠的神经毒性、肝毒性和肾毒性作用。

目前的研究是为了研究盐酸曲马多对成年雄性大鼠的大脑、肝脏和肾脏的毒性作用。40只成年雄性白化大鼠分为4组；第一个被视为对照组，其他人以 25、50 和 100 b.wt 口服给药。分别代表盐酸曲马多的治疗剂量、双倍治疗剂量和 4 倍治疗剂量，每天服用 1 个月。收集血清和脑、肝和肾组织用于生化和分子研究。Tramadol HCL 导致大脑血清素、8-羟基-2'-脱氧鸟苷 (8-OHdG) 和丙二醛 (MDA) 水平显着增加，同时还原型谷胱甘肽 (GSH)、过氧化氢酶 (CAT) 和超氧化物歧化酶 (SOD) 活性。在同一条线上，肝和肾 8-OHdG 和 MDA 水平显着增加，还原型谷胱甘肽 (GSH)、CAT 和 SOD 活性显着降低。此外，肝和肾功能参数包括血清丙氨酸氨基转移酶 (ALT)、天冬氨酸氨基转移酶 (AST)、尿素和肌酐以剂量依赖性方式增加。在分子水平上，肝细胞色素 P5402E1 (CYP2E1)、肾肾损伤分子 1 (KIM-1) 和金属蛋白酶组织抑制剂 1 (TIMP-1) 的表达水平也显着增加。脑的组织病理学评估证实了上述生化结果。总之，盐酸曲马多通过影响脑血清素水平和肝肾功能，以与其浓度相关的方式诱导神经毒性、肝毒性和肾毒性作用，