We examined the therapeutic effect of melatonin (MT) on cholestatic liver injury in rats with bile duct ligation (BDL). Cholestatic liver injury occurred 5 days after BDL and proceeded at 13 days, judging from the levels of serum hepatobiliary injury markers. Increases in the hepatic levels of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, and reduced glutathione (GSH) and the hepatic activity of myeloperoxidase (MPO), an index of tissue neutrophil infiltration, were observed 5 and 13 days after BDL. When MT at a dose of 10 or 100 mg/kg body weight was orally administered to rats with BDL everyday for one week, starting 6 days after BDL, a high dose of the indoleamine significantly attenuated cholestatic liver injury at 13 days after BDL. The daily administration of a high dose of MT significantly attenuated the increases in hepatic TBARS and GSH levels and MPO activity observed 13 days after BDL. These results indicate that MT administered orally at pharmacological doses exerts a therapeutic effect on cholestatic liver injury in rats with BDL possibly through its antioxidant and anti-inflammatory actions.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/978-1-4615-0135-0_64 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
In Vivo and In Vitro Models of Hepatic Fibrosis for Pharmacodynamic Evaluation and Pathology Exploration.
Int J Mol Sci
January 2025
College of Pharmacy and Food, Southwest Minzu University, Chengdu 610093, China.
Hepatic fibrosis (HF) is an important pathological state in the progression of chronic liver disease to end-stage liver disease and is usually triggered by alcohol, nonalcoholic fatty liver, chronic hepatitis viruses, autoimmune hepatitis (AIH), or cholestatic liver disease. Research on novel therapies has become a hot topic due to the reversibility of HF. Research into the molecular mechanisms of the pathology of HF and potential drug screening relies on reliable and rational biological models, mainly including animals and cells.
View Article and Find Full Text PDFUpdates in Biliary Atresia: Aetiology, Diagnosis and Surgery.
Children (Basel)
January 2025
Department of Paediatric Surgery, Kings College Hospital, Denmark Hill, London SE5 9RS, UK.
Biliary atresia (BA) is an obliterative disease of the bile ducts affecting between 1 in 10,000-20,000 infants with a predominance in Asian countries. It is clinically heterogeneous with a number of distinct variants (e.g.
View Article and Find Full Text PDFBilateral Renal Fungal Bezoars and Perinephric Abscess in an Infant With Arthrogryposis-Renal Dysfunction-Cholestasis Syndrome: A Clinico-pathologic Case Report.
Pediatr Dev Pathol
January 2025
Département d'Anatomie et Cytologie pathologiques, Hôpital Menzel Bourguiba, Menzel Bourguiba, Tunisia.
The patients with Arthrogryposis-Renal dysfunction-Cholestasis (ARC) syndrome have genetic susceptibility to the opportunistic infections due to the involvement of VPS33B (vacuolar protein sorting 33 homolog B) in phagolysosome fusion in macrophages. Detailed pathologic studies in ARC patients are missing in literature due to the lack of autopsy. We described the first autopsy case of ARC syndrome in a 2-month-old male infant.
View Article and Find Full Text PDFStudying the intracellular bile acid concentration and toxicity in drug-induced cholestasis: Comprehensive LC-MS/MS analysis with human liver slices.
Toxicol In Vitro
January 2025
University of Groningen, Groningen Research Institute of Pharmacy, Department of Pharmaceutical Technology and Biopharmacy, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands. Electronic address:
Drug-induced cholestasis (DIC) is a leading cause of drug-induced liver injury post-drug marketing, characterized by bile flow obstruction and toxic bile constituent accumulation within hepatocytes. This study investigates the toxicity associated with intracellular bile acid (BA) accumulation during DIC development. Using liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis, we examined intracellular BA concentrations in human precision-cut liver slices (PCLS) following the administration of cyclosporin A and chlorpromazine, both with and without an established BA mixture.
View Article and Find Full Text PDFActivation of S1PR2 on macrophages and the hepatocyte S1PR2/RhoA/ROCK1/MLC2 pathway in vanishing bile duct syndrome.
PLoS One
January 2025
Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Immunologic bile duct destruction is a pathogenic condition associated with vanishing bile duct syndrome (VBDS) after liver transplantation and hematopoietic stem-cell transplantation. As the bile acid receptor sphingosine 1-phosphate receptor 2 (S1PR2) plays a critical role in recruitment of bone marrow-derived monocytes/macrophages to sites of cholestatic liver injury, S1PR2 expression was examined using cultured macrophages and patient tissues. Bile canaliculi destruction precedes intrahepatic ductopenia; therefore, we focused on hepatocyte S1PR2 and the downstream RhoA/Rho kinase 1 (ROCK1) signaling pathway and bile canaliculi alterations using three-dimensional hepatocyte culture models that form obvious bile canaliculus-like networks.
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!