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

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Ayan Biswas ◽  
Suman Santra ◽  
Debasree Bishnu ◽  
Gopal Krishna Dhali ◽  
Abhijit Chowdhury ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Hepatic Fibrosis ◽  
Stellate Cell ◽  
Progressive Increase ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Stress Dependent ◽  
Liver Collagen

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.

scholarly journals Drug-Induced Autoimmune Hepatitis following Treatment with Zoledronic Acid

2017 ◽  
Vol 11 (2) ◽  
pp. 440-445 ◽  
Author(s):  
Jenny Sarah Schneider ◽  
Matteo Montani ◽  
Felix Stickel
Keyword(s):  
Liver Disease ◽  
Zoledronic Acid ◽  
Side Effects ◽  
Liver Injury ◽  
Drug Reactions ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
First Case ◽  
Alternative Drugs

Adverse drug reactions are among the most frequent side effects of synthetic and complementary alternative drugs and represent the premier causes of license revocations and acute liver failure. Drug-induced liver injury can resemble literally any other genuine liver disease and usually responds well to drug dechallenge. However, in some cases autoimmune-like hepatitis can evolve, requiring short- and sometimes long-term immunosuppression. Here, we present the hitherto first case of autoimmune-like hepatitis following treatment with zoledronic acid.

A Turn-on Probe for Detecting Antituberculotic Drug-induced Liver Injury in Mice via NIR-II Fluorescence/Optoacoustic Imaging

2021 ◽  
Author(s):  
Longqi Chen ◽  
Junjie Chen ◽  
Yichang Fang ◽  
Fang Zeng ◽  
Shuizhu Wu
Keyword(s):  
Infectious Disease ◽  
Liver Injury ◽  
Causes Of Death ◽  
Standard Treatment ◽  
Drug Induced ◽  
Optoacoustic Imaging ◽  
Drug Induced Liver Injury ◽  
Turn On

Standard treatment for tuberculosis (TB), an infectious disease and one of the top ten causes of death worldwide, usually lasts for a long term. And the antituberculotic-drug-induced liver injury has...

scholarly journals Long-Term Outcomes After Drug-Induced Liver Injury

2018 ◽  
Vol 17 (3) ◽  
pp. 292-299 ◽  
Author(s):  
Paul H. Hayashi ◽  
Einar S. Bjornsson
Keyword(s):  
Liver Injury ◽  
Long Term Outcomes ◽  
Drug Induced ◽  
Drug Induced Liver Injury

scholarly journals Long-term follow-up of patients with mild to moderate drug-induced liver injury

2007 ◽  
Vol 26 (1) ◽  
pp. 79-85 ◽  
Author(s):  
E. BJÖRNSSON ◽  
E. KALAITZAKIS ◽  
V. AV KLINTEBERG ◽  
N. ALEM ◽  
R. OLSSON
Keyword(s):  
Liver Injury ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Long Term Follow Up

scholarly journals Crocus sativus L. Extract Containing Polyphenols Modulates Oxidative Stress and Inflammatory Response against Anti-Tuberculosis Drugs-Induced Liver Injury

Plants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 167 ◽  
Author(s):  
Adil Farooq Wali ◽  
Jayachithra Ramakrishna Pillai ◽  
Yusra Al Dhaheri ◽  
Muneeb U. Rehman ◽  
Ambreen Shoaib ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Inflammatory Response ◽  
Hepatic Injury ◽  
Standard Dose ◽  
Crocus Sativus ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Response Status ◽  
Crocus Sativus L

The purpose of this study is to analyze the polyphenolic rich extract of Crocus sativus L. petals (CSP) in modulating liver oxidative stress and inflammatory response status against rifampicin isoniazid (INH-RIF) drug-induced liver injury. The INH-RIF was administered for 14 days with varying doses in Wistar rats, while silymarin was administered as standard dose. We report the defensive impacts of CSP against INH-RIF induced liver oxidative stress and proinflammatory cytokine. The CSP treatment at both doses significantly controlled all modulating biochemical hepatic injury indicators and resulted in the attenuation of arbitral INH-RIF damage. The components present in CSP identified by LC–ESI-Q-TOF–MS were found to be flavonoids and fatty acids. It can be inferred that CSP possesses a hepatoprotective capacity against INH-RIF-mediated hepatic injury, which may prove to be a medically beneficial natural product for the management of drug-induced liver injury.

scholarly journals ZnT8 Deficiency Protects From APAP-Induced Acute Liver Injury by Reducing Oxidative Stress Through Upregulating Hepatic Zinc and Metallothioneins

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen Su ◽  
Mingji Feng ◽  
Yuan Liu ◽  
Rong Cao ◽  
Yiao Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Serum Levels ◽  
Zinc Transporter ◽  
Hepatocyte Proliferation ◽  
Glycogen Depletion ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Cytochrome P450 Family ◽  
Jnk Activation

Zinc transporter 8 (ZnT8) is an important zinc transporter highly expressed in pancreatic islets. Deficiency of ZnT8 leads to a marked decrease in islet zinc, which is thought to prevent liver diseases associated with oxidative stress. Herein, we aimed to investigate whether loss of islet zinc affects the antioxidant capacity of the liver and acute drug-induced liver injury. To address this question, we treated ZnT8 knockout (KO) or wild-type control mice with 300 mg/ kg acetaminophen (APAP) or phosphate-buffered saline (PBS). Unexpectedly, we found that loss of ZnT8 in mice ameliorated APAP-induced injury and was accompanied by inhibition of c-Jun N-terminal kinase (JNK) activation, reduced hepatocyte death, and decreased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). An increase in hepatic glutathione (GSH) was observed, corresponding to a decrease in malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) levels. APAP-induced inflammation and glycogen depletion were alleviated. In contrast, no significant changes were observed in cytochrome P450 family 2 subfamily E member 1 (CYP2E1), the main enzyme responsible for drug metabolism. Elevated levels of hepatic zinc and metallothionein (MT) were also observed, which may contribute to the hepatoprotective effect in ZnT8 KO mice. Taken together, these results suggest that ZnT8 deficiency protects the liver from APAP toxicity by attenuating oxidative stress and promoting hepatocyte proliferation. This study provides new insights into the functions of ZnT8 and zinc as key mediators linking pancreatic and hepatic functions.

EZH2 Alleviates Antituberculosis Drug-Induced Liver Injury in Mice by Reducing H3K27 Trimethylation at the Nrf2 Promoter

2021 ◽  
Author(s):  
pei shengfei ◽  
luming yang ◽  
lin wang ◽  
xuelei gao ◽  
yu guo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Transcriptional Activation ◽  
Target Genes ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Preventative Measures ◽  
Oxidative Stress Pathway ◽  
Stress Pathway

Abstract BackgroundAnti-tuberculosis drug-induced liver injury (ADLI) limits the treatment of tuberculosis. The mechanisms underlying ADLI are unclear and there are no effective preventative measures to avoid this complication. MethodsIn this stuy, the protein contents of EZH2, Nrf2, NQO1 and HO-1 were detected by ELISA kit, while those of EZH2 and Nrf2 were determined by Western blot. The Chip experiment was used to detect the level of H3K27me3 in the Nrf2 promoter region.The liver were analyzed histopathologically in vivo using hematoxylin and eosin staining.ResultsHere we developed a murine model of ADLI that recapitulates liver injury in the human disease. Using this model, we investigated the potential involvement of the enhancer of zeste homolog 2 methyltransferase (EZH2), a histone methyltransferase which inhibits the transcriptional activation of the Nrf2-ARE oxidative stress pathway. Compared to controls, mice livers with ADLI showed decreased expression of EZH2 together with reduced H3K27me3 marks in the Nrf2 promoter. This was accompanied by increased expression of Nrf2 and its target genes NQO1 and HO-1. Liver injury in the mice with ADLI could be alleviated to an extent by in vivo delivery of siRNAs targeting EZH2, which further downregulated EZH2 expression and H3K27me3 levels in the Nrf2 promoter along with accompanying increases in Nrf2, NQO1 and HO-1 expression. ConclusionsTherefore, inhibiting EZH2 likely reduced liver damage in ADLI by enhancing this key anti-oxidative stress pathway. Our results establish a role for EZH2 in a mouse model of ADLI and furthermore provides valuable mechanistic insights into the development of ADLI pathology.

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