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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195633 | PMC |
| http://dx.doi.org/10.1155/2020/6987295 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Comprehensive profiling of serum microRNAs in normal and non-alcoholic fatty liver disease (NAFLD) patients.
Sci Rep
January 2025
Shaoxing Maternity and Child Health Care Hospital, No. 222 Fenglin East Road, Shaoxing, 312000, Zhejiang, China.
Pediatric non-alcoholic fatty liver disease (NAFLD) is emerging as a worldwide health concern with the potential to advance to cirrhosis and liver cancer. NAFLD can also directly contribute to heart problems through inflammation and insulin resistance, even in individuals without other risk factors. The pathological mechanisms of NAFLD are linked to functional differences of miRNAs in different biological environments.
View Article and Find Full Text PDFEfficacy and Safety of Dapagliflozin Compared to Pioglitazone in Diabetic and Non-Diabetic Patients with Non-alcoholic Steatohepatitis: A Randomized Clinical Trial.
Clin Res Hepatol Gastroenterol
January 2025
Department of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Egypt. Electronic address:
Background: Non-alcoholic steatohepatitis (NASH) is a serious end-stage spectrum of non-alcoholic fatty liver disease (NAFLD) with associated high risk of hepatic and extrahepatic complications. Several studies showed the significant beneficial effect of dapagliflozin on body composition, hepatic and metabolic parameters on NAFLD/NASH patients. The study aimed to investigate the efficacy and safety of dapagliflozin in both diabetic and non-diabetic biopsy-proven NASH patients; compared to pioglitazone.
View Article and Find Full Text PDFPredicting and managing liver fibrosis in biliary atresia.
Semin Pediatr Surg
January 2025
Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden. Electronic address:
Regardless of the underlying etiology and success of PE, progressive liver fibrosis and eventually cirrhosis represent the dominant pathology and the end-stage of BA. Ascending bile duct injury-induced cholestasis, inflammation and ductular reaction provide profibrogenic cytokine environment leading to myofibroblast activation and rapid progression of fibrosis especially after unsuccessful portoenterostomy. Although liver fibrosis and development of cirrhosis play a crucial role in determining BA outcomes, the exact prognostic significance and dynamics of mild to moderate liver fibrosis remain unclear.
View Article and Find Full Text PDFGeneration of a human induced pluripotent stem cell (iPSC) line ERPLi004-A from an Alpha-1 antitrypsin deficiency (AATD) patient with SERPINA1 mutation.
Stem Cell Res
January 2025
The University of Trans-Disciplinary Health Sciences and Technology, Bengaluru 560064, India; Eyestem Research, Centre for Cellular and Molecular Platforms (C-CAMP), Bengaluru 560065, India. Electronic address:
Alpha-1 antitrypsin deficiency (AATD) is an autosomal disorder that causes liver and lung disease. The risk of developing lung emphysema, chronic obstructive pulmonary disorder and liver cirrhosis is observed in >75 % people affected with a homozygous mutation. Here, we describe the generation of an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells (PBMC) isolated from a AATD patient using non viral and non-integrating episomal vectors.
View Article and Find Full Text PDFRoles of anoikis in hepatocellular carcinoma: mechanisms and therapeutic potential.
Med Oncol
January 2025
Department of Hepatobiliary Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Hepatocellular carcinoma (HCC), the most common primary liver cancer, is a highly aggressive malignancy with limited viable therapeutic options. For early HCC, resection surgery is currently the most effective treatment. However, in advanced stages, resection alone does not sufficiently address the disease, so finding a method with a better prognosis is necessary.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!