{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T06:47:58Z","timestamp":1782110878087,"version":"3.54.5"},"reference-count":68,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>2\u2010Ethylhexyl diphenyl phosphate (EHDPHP) is a widely used organophosphorus flame retardant frequently detected in environmental matrices and poses potential health risks. However, its cardiotoxic effects on mammalian cardiomyocytes and the underlying molecular mechanisms remain largely unclear. Niacin (NIA), an essential water\u2010soluble vitamin, exhibits potent antioxidant, anti\u2010inflammatory, and mitochondrial\u2010protective activities. In this study, we investigated EHDPHP\u2010induced toxicity in H9C2 cardiomyocytes and the protective effects of NIA. Cells were exposed to 100\u2009\u03bcM EHDPHP alone or in combination with 400, 600, and 800\u2009\u03bcM NIA. EHDPHP exposure significantly reduced cell viability, disrupted the balance between pro\u2010inflammatory cytokines (TNF\u2010\u03b1, IL\u20101\u03b2, IL\u20106, and IL\u201018) and the anti\u2010inflammatory cytokine IL\u201010, and induced oxidative stress, as evidenced by elevated ROS, MitoSOX, and MDA levels alongside decreased activities of antioxidant enzymes (SOD, GSH, GSH\u2010Px, and CAT). Additionally, EHDPHP disturbed mitochondrial dynamics by promoting fission and inhibiting fusion, impaired mitochondrial biogenesis via downregulation of AMPK and PGC\u20101\u03b1, triggered excessive mitophagy through PINK1, PRKN, and LC3 upregulation, and activated pyroptosis via GSDMD, NLRP3, and Caspase\u20101. Bioinformatics analyses confirmed the interconnected regulatory network among mitochondrial dynamics, mitophagy, pyroptosis, and inflammatory signaling in EHDPHP\u2010induced cardiomyocyte injury. Notably, NIA intervention dose\u2010dependently mitigated these detrimental effects, restoring cell viability, alleviating inflammation and oxidative stress, rebalancing mitochondrial fusion and fission, rescuing biogenesis, normalizing mitophagy, and inhibiting pyroptosis. These findings reveal a pathological cascade through which EHDPHP induces cardiomyocyte injury and demonstrate that NIA confers cardioprotection by targeting multiple pathological pathways. This study provides novel mechanistic insights into EHDPHP\u2010induced cardiotoxicity and highlights NIA as a promising nutritional intervention for reducing cardiovascular risks associated with environmental pollutants.<\/jats:p>","DOI":"10.1002\/jbt.70946","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:08:13Z","timestamp":1780337293000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Niacin Ameliorates EHDPHP\u2010Induced Oxidative Stress and Mitochondrial Dysfunction in H9C2 Cells"],"prefix":"10.1002","volume":"40","author":[{"given":"Lizhi","family":"Dai","sequence":"first","affiliation":[{"name":"Key Laboratory for Prevention and Control of Common Animal Diseases in General Higher Education Institutions of Heilongjiang Province, College of Veterinary Medicine Northeast Agricultural University Harbin 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Medicine Northeast Agricultural University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Prevention and Control of Common Animal Diseases in General Higher Education Institutions of Heilongjiang Province, College of Veterinary Medicine Northeast Agricultural University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youchong","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory for Prevention and Control of Common Animal Diseases in General Higher Education Institutions of Heilongjiang Province, College of Veterinary Medicine Northeast Agricultural University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Prevention and Control of Common Animal Diseases in General Higher Education Institutions of 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