Protective effect of ISO-1 with inhibition of RIPK3 up-regulation and neutrophilic accumulation on acetaminophen-induced liver injury in mice
Autor: | Osamu Maehara, Naoto Okubo, Jun Nishihira, Hiroshi Takeda, Tatsuya Ohkawara |
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Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine Neutrophils Acetates Liver injury Pharmacology Protective Agents RIPK3 Toxicology Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Animals Humans Macrophage Oxazoles Acetaminophen Macrophage migration inhibitory factor ISO 1 Chemistry Kinase digestive oral and skin physiology General Medicine medicine.disease Up-Regulation Mice Inbred C57BL 030104 developmental biology Chemical and Drug Induced Liver Injury Chronic Receptor-Interacting Protein Serine-Threonine Kinases Shock (circulatory) Models Animal ISO-1 medicine.symptom 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Toxicology Letters. 339:51-59 |
ISSN: | 0378-4274 |
Popis: | Overdose use of acetaminophen (APAP) often occurs a severe liver injury, and its liver injury is lethal in some cases. Macrophage migration inhibitory factor (MIF) is expressed in a variety of cells and has multifunctional roles. However, the role of MIF in APAP-induced liver injury has not been fully investigated. In this study, we investigated whether treatment with (S,R)-3-(4-hydroxyphenil)-4,5dihydro-5-isoxazole acetic acid methyl ester (ISO-1), a MIF inhibitor, protected mice from acute APAP-induced liver injury. Acute liver injury was induced by injection of APAP (300 mg/kg body weight). Mice were treated with a single injection of ISO-1(15 mg/kg body weight) 1 h (h) before APAP administration. Histological, biochemical and molecular analyses were performed in liver of mice 12 h after APAP administration. ISO-1 remarkably improved the histological findings of APAP-induced liver injury in mice. The increases in serum levels of alanine aminotransferase (ALT), and macrophage inflammatory protein-2 (MIP-2) by APAP were inhibited by ISO-1. In addition, ISO-1 reduced the increased number of the myeloperoxidase-staining cells and that of TUNEL-positive staining cells in the liver of mice with APAP-induced liver injury. Up-regulation of hepatic receptor interacting protein kinase (RIPK)3 and heat shock protein70 by APAP was suppressed in the liver of mice given ISO-1. These results provide the additional evidence that inhibition of MIF activity may be clinically effective for treatment of acute APAP-induced liver injury. (C) 2020 Elsevier B.V. All rights reserved. |
Databáze: | OpenAIRE |
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