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美沙酮摄入对大鼠肝脏组织的组织病理学研究及其对肝脏酶和炎症指标的影响

Histopathological study of liver tissue due to methadone consumption and its effect on liver enzymes and inflammatory indices in rat.

作者信息

Amraei Mansour, Mohamadpour Mahmoud, Ahmadi Mohammad Reza Hafezi, Azizi Monireh, Daemi Ahmad, Omidi Mohammad, Shirzadpour Ehsan

机构信息

Department of Physiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.

Department of Biochemistry, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran,

出版信息

Drug Des Devel Ther. 2018 Nov 5;12:3785-3795. doi: 10.2147/DDDT.S182032. eCollection 2018.

Abstract

BACKGROUND

Methadone (MET)-based treatment is currently one of the best known approaches in the treatment of opioid dependence. It is claimed that MET use exerts adverse effects on the performance of some organs, especially liver. Thus, the present study aims to investigate MET effects on the hepatic tissue as well as its effect on the hepatic enzyme levels and inflammatory markers in rats.

MATERIALS AND METHODS

Twenty-eight mature male Wistar rats underwent an 8-week treatment in four equal groups including the control group (an ordinary daily dietary regime) as well as the experimental groups 1, 2, and 3 (an ordinary daily dietary regime and gavage-fed on MET syrup for 5, 20, and 40 mg/kg body weight per day). Blood samples were collected from all rats in the beginning and end of the study to measure their hepatic enzyme levels and inflammatory markers. In the end, their livers were subjected to histological examinations.

RESULTS

The mean serum levels of hepatic enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) increased considerably across all the three groups that had received various dosages of MET (5, 20, and 40 mg/kg) in the end of the study as compared to the beginning of the study (<0.001). It was also found that the inflammatory indicators (interleukin-6, tumor necrosis factor-alpha, and C-reactive protein) rose significantly in the groups that had received various dosages of MET in contrast to the control group (<0.01, <0.001, and <0.001, respectively). The histopathological images of the liver cross-sections revealed dosage-dependent tissue changes in the groups that had received various dosages of MET.

CONCLUSION

The present study tried to prove the adverse effects of MET in the development of liver damage. Since MET-based treatment is frequently prescribed by physicians for curing the addiction to narcotics, better strategies are required for its correct usage.

摘要

背景

美沙酮(MET)治疗目前是阿片类药物依赖治疗中最知名的方法之一。据称,使用美沙酮会对某些器官,尤其是肝脏的功能产生不利影响。因此,本研究旨在调查美沙酮对大鼠肝组织的影响及其对肝酶水平和炎症标志物的影响。

材料与方法

28只成年雄性Wistar大鼠分为四组,进行为期8周的治疗,包括对照组(普通日常饮食方案)以及实验组1、2和3(普通日常饮食方案,并每天按5、20和40mg/kg体重灌喂美沙酮糖浆)。在研究开始和结束时从所有大鼠采集血样,以测量其肝酶水平和炎症标志物。最后,对它们的肝脏进行组织学检查。

结果

在研究结束时,与研究开始时相比,接受不同剂量美沙酮(5、20和40mg/kg)的所有三组大鼠的肝酶(丙氨酸转氨酶、天冬氨酸转氨酶和碱性磷酸酶)平均血清水平均显著升高(<0.001)。还发现,与对照组相比,接受不同剂量美沙酮的组中炎症指标(白细胞介素-6、肿瘤坏死因子-α和C反应蛋白)显著升高(分别为<0.01、<0.001和<0.001)。肝脏横截面的组织病理学图像显示,接受不同剂量美沙酮的组中存在剂量依赖性组织变化。

结论

本研究试图证明美沙酮在肝损伤发展中的不利影响。由于医生经常开以美沙酮为基础的治疗方法来治疗麻醉品成瘾,因此需要更好的策略来正确使用它。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a924/6225910/198c88d416aa/dddt-12-3785Fig1.jpg

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