Isoniazid and Rifampicin Produce Hepatic Fibrosis through an Oxidative Stress-Dependent Mechanism.

IF 1.5 Q3 GASTROENTEROLOGY & HEPATOLOGY

International Journal of Hepatology Pub Date : 2020-04-23 eCollection Date: 2020-01-01 DOI:10.1155/2020/6987295

Ayan Biswas, Suman Santra, Debasree Bishnu, Gopal Krishna Dhali, Abhijit Chowdhury, Amal Santra

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引用次数: 14

Abstract

Methods: A combined dose of INH (50 mg) and RMP (100 mg) per kg body weight per day was administered to mice by oral gavage, 6 days a week, for 4 to 24 weeks for the assessment of liver injury, oxidative stress, and development of hepatic fibrosis, including demonstration of changes in key fibrogenesis linked pathways and mediators.

Results: Progressive increase in markers of hepatic stellate cell (HSC) activation associated with changes in matrix turnover was observed between 12 and 24 weeks of INH-RMP treatment along with the elevation of liver collagen content and significant periportal fibrosis. These were associated with concurrent apoptosis of the hepatocytes, increase in hepatic cytochrome P450 2E1 (CYP2E1), NADPH oxidase (NOX) activity, and development of hepatic oxidative stress.

Conclusions: INH-RMP can activate HSC through generation of NOX-mediated oxidative stress, leading to the development of liver fibrosis.

Abstract Image

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异烟肼和利福平通过氧化应激依赖机制产生肝纤维化。

方法:小鼠每天口服每公斤体重50 mg INH和100 mg RMP，每周6天，持续4至24周，以评估肝损伤、氧化应激和肝纤维化的发展，包括证明关键纤维化相关途径和介质的变化。结果:在INH-RMP治疗12至24周期间，观察到与基质转换变化相关的肝星状细胞(HSC)活化标志物的进行性增加，同时肝脏胶原含量升高和明显的门脉周围纤维化。这些都与肝细胞的同步凋亡、肝细胞色素P450 2E1 (CYP2E1)、NADPH氧化酶(NOX)活性的增加和肝氧化应激的发生有关。结论:INH-RMP可通过产生nox介导的氧化应激激活HSC，导致肝纤维化的发生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Hepatology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

3.80

自引率

0.00%

发文量

审稿时长

15 weeks

期刊介绍： International Journal of Hepatology is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies related to the medical, surgical, pathological, biochemical, and physiological aspects of hepatology, as well as the management of disorders affecting the liver, gallbladder, biliary tree, and pancreas.