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阿扑吗啡对大鼠扑热息痛诱导的肝毒性的影响。

The effects of apomorphine on paracetamol-induced hepatotoxicity in rats.

作者信息

Sehitoglu Muserref Hilal, Yayla Muhammet, Kiraz Asli, Oztopuz Rahime Ozlem, Bayir Yasin, Karaca Turan, Khalid Sumbul, Akpinar Erol

机构信息

Department of Biochemistry, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey.

Department of Pharmacology, Faculty of Medicine, Kars Kafkas University, Kars, Turkey.

出版信息

Cell Mol Biol (Noisy-le-grand). 2017 Dec 30;63(12):40-44. doi: 10.14715/cmb/2017.63.12.10.

Abstract

It is becoming progressively more understandable that overdose of paracetamol in both humans and animals causes severe hepatotoxicity. Apomorphine is known as a neuroprotective agent. Due to the protective effect,  apomorphine had been tested in experimental studies on different models. Findings obtained through series of expriments suggested that apomorphine may also be useful in liver toxicity. The aim of this study is to investigate the relationship among the hepatoprotective mechanism of apomorphine and to determine the possible role of apomorphine on paracetamol-induced hepatotoxicity in rats. 30 Sprague Dawley rats (adult male) were distributed into 5 groups. Group 1 was the control group and did not receive any medication. Group 2 received only paracetamol 2 g/kg by intragastric gavage to induce hepatotoxicity. Groups 3 and 4 were given apomorphine 1 mg/kg and 2 mg/kg by intraperitoneal injection, respectively. Groups 3 and 4 were given 2g/kg  of Paracetamol. In Group 5, rats were treated with 2 mg/kg of apomorphine. Drug-treated rats were given food for the next 24 h until they were sacrified. Moreover, we also performed AST, ALT measurements in serum, MDA and SOD levels in liver tissues and histopathological analysis of the liver in all groups. Apomorphine had positive effects on both liver enzymes, oxidative stress markers and histopathological results in paracetamol-induced hepatotoxicity. Additionally, apomorphine at 2 mg/kg dose was significantly more protective as compared to 1 mg/kg as evidenced by the histopathological examination results. It was thought that apomorphine was found hepatoprotective on paracetamol-induced hepatotoxicity, especially at higher doses such as 2 mg/kg.

摘要

扑热息痛在人类和动物体内过量服用会导致严重的肝毒性,这一点越来越容易理解。阿扑吗啡是一种神经保护剂。由于其保护作用,已在不同模型的实验研究中对阿扑吗啡进行了测试。一系列实验获得的结果表明,阿扑吗啡可能对肝脏毒性也有作用。本研究的目的是探讨阿扑吗啡的肝保护机制之间的关系,并确定阿扑吗啡在大鼠扑热息痛诱导的肝毒性中可能发挥的作用。将30只成年雄性Sprague Dawley大鼠分为5组。第1组为对照组,未接受任何药物治疗。第2组仅通过灌胃给予2 g/kg扑热息痛以诱导肝毒性。第3组和第4组分别通过腹腔注射给予1 mg/kg和2 mg/kg阿扑吗啡。第3组和第4组给予2 g/kg扑热息痛。第5组大鼠用2 mg/kg阿扑吗啡治疗。给药后的大鼠在接下来的24小时内给予食物,直至处死。此外,我们还对所有组的血清AST、ALT水平、肝组织中的MDA和SOD水平进行了测量,并对肝脏进行了组织病理学分析。阿扑吗啡对扑热息痛诱导的肝毒性中的肝酶、氧化应激标志物和组织病理学结果均有积极影响。此外,组织病理学检查结果表明,2 mg/kg剂量的阿扑吗啡比1 mg/kg具有更显著的保护作用。据认为,阿扑吗啡对扑热息痛诱导的肝毒性具有肝保护作用,尤其是在2 mg/kg等较高剂量时。

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