Drug-induced liver injury is a growing concern for pharmaceutical companies and patients because numerous drugs have been linked to hepatotoxicity and it is the most common reason for a drug to be withdrawn. Flutamide rarely causes liver dysfunction in humans, and immune allergic reactions have been suggested in some cases. In this study, we investigated the mechanisms of flutamide-induced liver injury in BALB/c mice. Plasma alanine aminotransferase and aspartate aminotransferase levels were significantly increased 3, 6 and 9 h after flutamide (1500 mg kg⁻¹ , p.o.) administration. The biomarker for oxidative stress was not changed, but Th2-dominant immune-related factors, such as interleukin (IL)-4, IL-5, STAT6 and GATA-binding protein (GATA)-3, were induced in flutamide-administered mice. The pre-administration of monoclonal-IL-4 antibody suppressed the hepatotoxicity of flutamide. In addition, we investigated the effect of 13,14-dihydro-15-keto-PGD₂ (DK-PGD₂; 10 µg per mouse, i.p.) administration on flutamide-induced acute liver injury. Coadministration of DK-PGD₂ and flutamide resulted in a significant increase in alanine aminotransferase and a remarkable increase of macrophage inflammatory protein-2. In conclusion, we demonstrated that flutamide-induced acute liver injury is mediated by Th2-dominant immune responses in mice.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/jat.1706 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Drug repositioning of mesalamine via supramolecular nanoassembly for the treatment of drug-induced acute liver failure.
Theranostics
January 2025
Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
Acute liver failure (ALF) is characterized by rapid hepatic dysfunction, primarily caused by drug-induced hepatotoxicity. Due to the lack of satisfactory treatment options, ALF remains a fatal clinical disease, representing a grand challenge in global health. For the drug repositioning to ALF of mesalamine, which is clinically approved for the treatment of inflammatory bowel disease (IBD), we propose a supramolecular prodrug nanoassembly (SPNs).
View Article and Find Full Text PDFEmodin induced hepatic steatosis in BALb/c mice by modulating the gut microbiota composition and fatty acid metabolism.
Front Pharmacol
December 2024
School of Agriculture and Biology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong, China.
Introduction: The aim of this study is to examine the physiological effects of emodin on intestinal microorganisms and the liver in the BALb/c mice.
Method And Results: Following an 8-week administration of emodin at doses of 25, 50, and 100 mg/kg/day,pathological analyses revealed that emodin significantly reduced the colon length, induced colonic crypt inflammation,diminished the colonic mucus layer,and decreased the fluorescence intensity of colonic tight junction proteins ZO-1 and Occludin. Concurrently, 16S rDNA gene sequencing corroborated that emodin altered the diversity and composition of the intestinal microbiota by increasing the to ratio.
Relevance of perioperative fluid dynamics in liver transplantation to acute kidney injury and patient outcomes: a cross-sectional survey.
J Pharm Policy Pract
December 2024
Department of Clinical Pharmacy, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People's Republic of China.
Background: Fluid administration is a critical component of perioperative management for liver transplant recipients, and excessive fluid infusion can lead to acute kidney injury (AKI) and poor patient outcomes.
Method: We conducted a cross-sectional survey on the fluid intake and output of adult liver transplant recipients over a 7-day period. The patients were divided into AKI and non-AKI groups.
Iristectorin A Ameliorates Cisplatin-Induced Hepatorenal Injury in Mice Through Modulation of the Nrf2/HO-1 Signaling Pathway.
J Biochem Mol Toxicol
January 2025
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey.
Cisplatin (CIS) is a chemotherapeutic agent frequently used in cancer treatment. However, depending on the dosage and duration of use, CIS can lead to hepatotoxicity and nephrotoxicity. Iristectorin A (IRIS), a natural flavonoid, has been found to exhibit antioxidant and protective effects.
View Article and Find Full Text PDFAbsence of Viral Replication Is Associated With Improved Outcome in Anti-HCV-Positive Patients With Hepatocellular Carcinoma.
Liver Int
February 2025
Italian Liver Cancer (ITA.LI.CA) Association, Bologna, Italy.
Background And Aims: Presence of active hepatitis C virus (HCV) infection may influence the outcome of patients treated for hepatocellular carcinoma (HCC), although this issue has never been adequately assessed in a large series of patients. The aim of this study was to evaluate whether the presence of active HCV affects the survival of patients treated for HCC.
Methods: This study assessed the outcome of 3123 anti-HCV-positive patients with HCC, subdivided according to the presence of active HCV infection or previous sustained virological response (SVR).
Want 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!