The aim of this study was to illustrate the initial subclinical drug-induced liver injury and the associated adaptive immune response by monitoring for the changes in plasma IL-2, IL-10, and some cytochrome P450 activity during chronic administration of nevirapine (NVP), isoniazid (INH), and paracetamol (PAR) in rats without clinical hepatotoxicity. Male Sprague-Dawley (SD) rats were divided into four groups (saline (S), NVP, INH, and PAR) of 25 animals each. The drugs were administered daily for 42 days at therapeutic doses (NVP 200 mg/kg, PAR 500 mg/kg, and INH 20 mg/kg) to the respective groups by oral gavage and five rats per group were sacrificed weekly. All the three drugs induced a subclinical liver injury in the first 2-3 weeks followed by healing, indicating adaption. The liver injury was pathologically similar and was associated with immune stimulation and increased cytochrome P450 activity. NVP- and PAR-induced liver injury lasted up to 14 days while that for INH lasted for 28 days. NVP-induced liver injury was associated with increased IL-2, CD4 count, and CYP3A2 activity, followed by increased IL-10 during the healing phase. In conclusion, the initial drug-induced subclinical liver injury, its spontaneous healing, and the associated adaptive immune response have been demonstrated.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136381 | PMC |
| http://dx.doi.org/10.1155/2016/3094783 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Hepatotoxicity of statins: a real-world study based on the US Food and Drug Administration Adverse Event Reporting System database.
Front Pharmacol
January 2025
Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Background: Statins, as an important class of lipid-lowering drugs, play a key role in the prevention and treatment of cardiovascular diseases. However, with their widespread use in clinical practice, some adverse events have gradually emerged. In particular, the hepatotoxicity associated with statins use has become one of the clinical concerns that require sufficient attention.
View Article and Find Full Text PDFSerum proteomic and metabolomic profiling of hepatocellular carcinoma patients co-infected with .
Front Immunol
January 2025
Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning, China.
Background: () infection is a significant risk factor for hepatocellular carcinoma (HCC), yet its underlying mechanisms remain poorly understood. This study aimed to investigate the impact of infection on the serum proteomic and metabolomic profiling of HCC patients, focusing on the potential mechanisms.
Method: A retrospective clinical analysis was conducted on 1121 HCC patients, comparing those with and without infection.
Advanced 3D bioprinted liver models with human-induced hepatocytes for personalized toxicity screening.
J Tissue Eng
January 2025
Engineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Tianjin Institutes of Health Science, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
The development of advanced models for assessing liver toxicity and drug responses is crucial for personalized medicine and preclinical drug development. 3D bioprinting technology provides opportunities to create human liver models that are suitable for conducting high-throughput screening for liver toxicity. In this study, we fabricated a humanized liver model using human-induced hepatocytes (hiHeps) derived from human fibroblasts via a rapid and efficient reprogramming process.
View Article and Find Full Text PDFHigh mobility group box1 as a danger signal inducing the infiltration of neutrophils and macrophages in thioacetamide-induced rat liver injury.
J Toxicol Pathol
January 2025
Laboratory of Veterinary Pathology, Osaka Metropolitan University, 1-58 Rinku-Ourai-Kita, Izumisano City, Osaka 598-8531, Japan.
The liver, a major organ involved in substance metabolism, is highly susceptible to toxicity induced by chemicals and their metabolites. Although damage-associated molecular patterns (DAMPs) have been implicated in the development of sterile inflammation following cell injury, their involvement in chemically induced hepatocellular injury remains underexplored. This study aimed to determine the role of high-mobility group box 1 (HMGB1), a DAMP, in a rat model of liver injury treated with thioacetamide, a hepatotoxicant.
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!