Adikwu Elias, Bokolo Bonsome
Department of Pharmacology, Faculty of Basic Medical Sciences, University of Port Harcourt, Choba, Rivers State, Nigeria.
Department of Pharmacology, Faculty of Basic Medical Sciences, Niger Delta University Wilberforce Island, Bayelsa State, Nigeria.
Adv Pharm Bull. 2017 Sep;7(3):367-374. doi: 10.15171/apb.2017.044. Epub 2017 Sep 25.
The therapeutic benefit derived from the clinical use of tramadol (TD) has been characterized by hepatotoxicity due to misuse and abuse. The implications of drug-induced hepatotoxicity include socio-economic burden which makes the search for remedy highly imperative. The present study investigated the protective effects of melatonin (MT) and n-acetylcysteine (NAC) on TD-induced hepatotoxicity in albino rats. Forty five adult rats used for this study were divided into nine groups of five rats each. The rats were pretreated with 10mg/kg/day of NAC, 10mg/kg/day of MT and combined doses of NAC and MT prior to the administration of 15 mg/kg/day of TD intraperitoneally for 7 days respectively. At the termination of drug administration, rats were weighed, sacrificed, and serum was extracted and evaluated for liver function parameters. The liver was harvested, weighed and evaluated for oxidative stress indices and liver enzymes. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, total bilirubin, conjugated bilirubin, and malondialdehyde levels were significantly (P<0.05) increased in rats administered with TD when compared to control. Furthermore, glutathione, superoxide dismutase and catalase levels were decreased significantly (P<0.05) in rats administered with TD when compared to control. The Liver of TD-treated rats showed necrosis of hepatocytes. However, the observed biochemical and liver histological alterations in TD-treated rats were attenuated in NAC and MT pretreated rats. Interestingly, pretreatment with combined doses of NAC and MT produced significant (P<0.05) effects on all evaluated parameters in comparison to their individual doses. Based on the findings in this study, melatonin and n- acetylcysteine could be used clinically as remedies for tramadol associated hepatotoxity.
曲马多（TD）临床使用所带来的治疗益处因误用和滥用而表现为肝毒性。药物性肝毒性的影响包括社会经济负担，这使得寻找补救措施迫在眉睫。本研究调查了褪黑素（MT）和N-乙酰半胱氨酸（NAC）对TD诱导的白化大鼠肝毒性的保护作用。本研究使用的45只成年大鼠分为9组，每组5只。在分别腹腔注射15mg/kg/天的TD共7天之前，大鼠分别用10mg/kg/天的NAC、10mg/kg/天的MT以及NAC和MT的联合剂量进行预处理。在药物给药结束时，对大鼠称重、处死，提取血清并评估肝功能参数。摘取肝脏，称重并评估氧化应激指标和肝酶。与对照组相比，给予TD的大鼠丙氨酸氨基转移酶、碱性磷酸酶、天冬氨酸氨基转移酶、总胆红素、结合胆红素和丙二醛水平显著（P<0.05）升高。此外，与对照组相比，给予TD的大鼠谷胱甘肽、超氧化物歧化酶和过氧化氢酶水平显著（P<0.05）降低。TD处理大鼠的肝脏显示肝细胞坏死。然而，在NAC和MT预处理的大鼠中，TD处理大鼠中观察到的生化和肝脏组织学改变有所减轻。有趣的是，与它们的单独剂量相比，NAC和MT联合剂量预处理对所有评估参数均产生显著（P<0.05）影响。基于本研究的结果，褪黑素和N-乙酰半胱氨酸可在临床上用作曲马多相关肝毒性的补救措施。
