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This study aims to investigate the protective effect of oxycodone in myocardial injury of lipopolysaccharide\u2010induced sepsis and its related signalling pathways. Wild\u2010type and nuclear factor erythroid 2\u2010related factor 2 (Nrf2)\u2010knockout mice, as well as H9c2 cardiomyocytes cultures treated with lipopolysaccharide (LPS) were used as models of septic myocardial injury. H9c2 cardiomyocytes culture showed that oxycodone protected cells from pyroptosis induced by LPS. Mice model confirmed that oxycodone pretreatment significantly attenuated myocardial pathological damage and improved cardiac function demonstrated by increased ejection fraction (EF) and fractional shortening (FS), as well as decreased cardiac troponin I (cTnI) and creatine kinase isoenzymes MB (CK\u2010MB). Oxycodone also reduced the levels of inflammatory factors and oxidative stress damage induced by LPS, which involves pyroptosis\u2010related proteins including: Nod\u2010like receptor protein 3 (NLRP3), Caspase 1, Apoptosis\u2010associated speck\u2010like protein contain a CARD (ASC), and Gasdermin D (GSDMD). These changes were mediated by Nrf2 and heme oxygenase\u20101 (HO\u20101) because Nrf2\u2010knockout mice or Nrf2 knockdown in H9c2 cells significantly reversed the beneficial effect of oxycodone on oxidative stress, inflammatory responses and NLRP3\u2010mediated pyroptosis. Our findings yielded that oxycodone therapy reduces LPS\u2010induced myocardial injury by suppressing NLRP3\u2010mediated pyroptosis via the Nrf2\/HO\u20101 signalling pathway in vivo and in vitro.<\/jats:p>","DOI":"10.1111\/1440-1681.13910","type":"journal-article","created":{"date-parts":[[2024,7,28]],"date-time":"2024-07-28T23:14:27Z","timestamp":1722208467000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Oxycodone attenuates lipopolysaccharide\u2010induced myocardial injury by inhibiting inflammation, oxidation and pyroptosis via Nrf2\/<scp>HO<\/scp>\u20101 signalling pathway"],"prefix":"10.1111","volume":"51","author":[{"given":"Yanting","family":"Wang","sequence":"first","affiliation":[{"name":"The First Central Clinical College Tianjin Medical University  Tianjin 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