{"title":"Protective Role of Oxycodone in Myocardial Oxidative Stress and Mitochondrial Dysfunction Induced by Ischemia-Reperfusion","authors":"Yongzheng Jiang, Hua He, Xinwei Jia","doi":"10.1002/jbt.70151","DOIUrl":null,"url":null,"abstract":"<p>Ischemia-reperfusion (I/R) injury is a significant clinical problem impacting the heart and other organs, such as the kidneys and liver. This study explores the protective effects of oxycodone on myocardial I/R injury and its underlying mechanisms. Using a myocardial I/R model in Sprague-Dawley (SD) rats and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in H9c2 cells, we administered oxycodone and inhibited AMP-activated protein kinase (AMPK) with Compound C (C.C). Our results showed that oxycodone significantly reduced lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) production while stabilizing mitochondrial membrane potential (MMP). Western blot and RT-qPCR analyzes confirmed that oxycodone enhances AMPK phosphorylation and upregulates the expression of Silent Information Regulator 1 (SIRT1) and Peroxisome Proliferator-Activated Receptor γ Coactivator 1α (PGC-1α), thereby protecting myocardial cells. These findings suggest that oxycodone exerts significant protective effects against I/R injury by activating the AMPK pathway, offering new potential therapeutic targets for myocardial protection.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70151","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70151","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Ischemia-reperfusion (I/R) injury is a significant clinical problem impacting the heart and other organs, such as the kidneys and liver. This study explores the protective effects of oxycodone on myocardial I/R injury and its underlying mechanisms. Using a myocardial I/R model in Sprague-Dawley (SD) rats and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in H9c2 cells, we administered oxycodone and inhibited AMP-activated protein kinase (AMPK) with Compound C (C.C). Our results showed that oxycodone significantly reduced lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) production while stabilizing mitochondrial membrane potential (MMP). Western blot and RT-qPCR analyzes confirmed that oxycodone enhances AMPK phosphorylation and upregulates the expression of Silent Information Regulator 1 (SIRT1) and Peroxisome Proliferator-Activated Receptor γ Coactivator 1α (PGC-1α), thereby protecting myocardial cells. These findings suggest that oxycodone exerts significant protective effects against I/R injury by activating the AMPK pathway, offering new potential therapeutic targets for myocardial protection.
期刊介绍:
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.