Isoniazid and Rifampicin Produce Hepatic Fibrosis through an Oxidative Stress-Dependent Mechanism
Joint Authors
Biswas, Ayan
Santra, Suman
Bishnu, Debasree
Dhali, Gopal Krishna
Chowdhury, Abhijit
Santra, Amal
Source
International Journal of Hepatology
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-04-23
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Background & Aims.
Chronic hepatitis (CH) has emerged as a distinct outcome of drug-induced liver injury (DILI).
Combination therapy of Isoniazid (INH) and Rifampicin (RMP) which is widely used for prolonged periods can cause acute hepatotoxicity and has been also incriminated in chronic DILI.
We sought evidence of the production of hepatic fibrosis on long-term INH-RMP treatment through experiments in BALB/c mice exposed to INH-RMP.
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.
American Psychological Association (APA)
Biswas, Ayan& Santra, Suman& Bishnu, Debasree& Dhali, Gopal Krishna& Chowdhury, Abhijit& Santra, Amal. 2020. Isoniazid and Rifampicin Produce Hepatic Fibrosis through an Oxidative Stress-Dependent Mechanism. International Journal of Hepatology،Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1171459
Modern Language Association (MLA)
Biswas, Ayan…[et al.]. Isoniazid and Rifampicin Produce Hepatic Fibrosis through an Oxidative Stress-Dependent Mechanism. International Journal of Hepatology No. 2020 (2020), pp.1-12.
https://search.emarefa.net/detail/BIM-1171459
American Medical Association (AMA)
Biswas, Ayan& Santra, Suman& Bishnu, Debasree& Dhali, Gopal Krishna& Chowdhury, Abhijit& Santra, Amal. Isoniazid and Rifampicin Produce Hepatic Fibrosis through an Oxidative Stress-Dependent Mechanism. International Journal of Hepatology. 2020. Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1171459
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1171459