{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:19:20Z","timestamp":1788401960347,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:00:00Z","timestamp":1701993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bardoxolone methyl, which triggers nuclear factor erythroid 2\u2010related factor (Nrf2), has therapeutic effects against myocardial infarction, heart failure, and other diseases. Nrf2 can inhibit the activation of the thioredoxin\u2010interacting protein (TXNIP)\/NLR family pyrin domain\u2010containing protein 3 (NLRP3) pathway. Doxorubicin is an anthracycline chemotherapeutic drug associated with cardiotoxicity, limiting its clinical use. In this study, we explored the specific mechanism of the Nrf2\u2013TXNIP\u2013NLRP3 pathway in doxorubicin\u2010induced cardiotoxicity using bardoxolone methyl in animal and cell models. Using in vivo and in vitro experiments, we show that doxorubicin can induce oxidative stress and pyroptosis in the heart. Western blot and co\u2010immunoprecipitation experimental results found that doxorubicin can reduce the interaction between TXNIP and TRX, increase the interaction between TXNIP and NLRP3, and activate the pyroptosis process. Bardoxolone methyl reduces the accumulation of reactive oxygen species in cardiomyocytes through the Nrf2 pathway, inhibits the interaction between TXNIP and NLRP3, and alleviates the progression of myocardial damage and cardiac fibrosis. Bardoxolone methyl lost its therapeutic effect when the expression of Nrf2 was decreased. Additionally, repressing the expression of TXNIP can inhibit the activation of NLRP3 and alleviate myocardial damage caused by doxorubicin. Collectively, our findings confirm that bardoxolone methyl alleviates doxorubicin\u2010induced cardiotoxicity by activating Nrf2 and inhibiting the TXNIP\u2013NLRP3 pathway.<\/jats:p>","DOI":"10.1002\/tox.24075","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T17:07:44Z","timestamp":1702055264000},"page":"1936-1950","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Bardoxolone methyl attenuates doxorubicin\u2010induced cardiotoxicity by inhibiting the <scp>TXNIP\u2013NLRP3<\/scp> pathway through Nrf2 activation"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2171-9271","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine The First Affiliated Hospital of Bengbu Medical College  Bengbu Anhui 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