Vitamin E supplementation ameliorates the hepatotoxicity induced by Tramadol: toxicological, histological and immunohistochemical study

IF 2.8 4区医学 Q2 TOXICOLOGY Toxicology Mechanisms and Methods Pub Date : 2020-03-01 DOI:10.1080/15376516.2019.1681043

M. A. Ibrahim, H. Ibrahim, Alaa A. Mohamed, H. G. Tammam

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引用次数: 10

Abstract

Abstract Several deleterious effects of Tramadol including deaths were reported especially when used in large doses. Being metabolized mainly in the liver, Tramadol have serious hepatotoxic effects. This study investigates the effect of vitamin E on Tramadol-induced hepatotoxicity in rats by evaluating the antioxidant biochemical markers, the histopathological and immunohistochemical changes.Thirty adult mature male albino rats were divided into five groups (Gs); G1: negative control; G2: received Tramadol 150 mg/kg, G 3–5: received Tramadol plus vitamin E in concentrations of 50 mg/kg, 100 mg/kg and 200 mg/kg respectively. Liver function parameters and oxidative markers in liver tissue (CAT, SOD, GSH, and MDA) were estimated. Liver samples were processed for histopathological and immunohistochemical (Caspase 3 and TNF) examinations. The results indicated that Sub-chronic administration of Tramadol resulted in impaired liver functions, increased oxidative stress parameters with decreased antioxidant capacity of liver tissues, severe hepatocellular damage (hydropic degeneration, steatosis and apoptosis) and strong immunoexpression to TNF and Caspase 3. All these effects were ameliorated with concomitant administration of vitamin E especially with high doses. The co-treatment of Tramadol-intoxicated rats with Vitamin E, especially in high doses, protects against hepatic toxicity.

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补充维生素E改善曲马多肝毒性的毒理学、组织学和免疫组织化学研究

摘要报道了曲马多的几种有害作用，包括死亡，尤其是在大剂量使用时。曲马多主要在肝脏代谢，具有严重的肝毒性作用。本研究通过评估抗氧化生化标志物、组织病理学和免疫组织化学变化，探讨维生素E对曲马多诱导的大鼠肝毒性的影响。将30只成年雄性白化大鼠分为5组（Gs）；G1：阴性对照；G2：接受曲马多150 mg/kg，G 3–5：接受曲马多加维生素E，浓度为50 mg/kg，100 mg/kg和200 mg/kg。评估肝功能参数和肝组织中的氧化标记物（CAT、SOD、GSH和MDA）。对肝脏样本进行组织病理学和免疫组织化学（Caspase 3和TNF）检查。结果表明，曲马多的亚慢性给药导致肝功能受损，氧化应激参数增加，肝组织抗氧化能力下降，严重的肝细胞损伤（水肿变性、脂肪变性和细胞凋亡）以及TNF和Caspase 3的强免疫表达。所有这些效果都通过同时服用维生素E而得到改善，尤其是在高剂量的情况下。曲马多中毒大鼠与维生素E联合治疗，尤其是高剂量治疗，可防止肝毒性。

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来源期刊

Toxicology Mechanisms and Methods TOXICOLOGY-

自引率

3.10%

发文量

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.