{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:30:47Z","timestamp":1792729847402,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":273,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:p><jats:bold>Background and purpose:<\/jats:bold> The clinical use of arsenic trioxide (As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>), a potent antineoplastic agent, is limited by its severe cardiotoxic effects. QT interval prolongation and apoptosis have been implicated in the cardiotoxicity of As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>. The present study was designed to evaluate the effects of resveratrol on As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>\u2010induced apoptosis and cardiac injury.<\/jats:p><jats:p><jats:bold>Experimental approach:<\/jats:bold> In a mouse model of As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>\u2010induced cardiomyopathy <jats:italic>in vivo<\/jats:italic>, QT intervals and plasma enzyme activities were measured; cardiac tissues were examined histologically and apoptosis assessed. In H9c2 cardiomyocyte cells, viability, apoptosis, generation of reactive oxygen species (ROS) and cellular calcium levels were measured.<\/jats:p><jats:p><jats:bold>Key results:<\/jats:bold> In the mouse model, resveratrol reduced As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>\u2010induced QT interval prolongation and cardiomyocyte injury (apoptosis, myofibrillar loss and vacuolization). In addition, increased lactate dehydrogenase activity and decreased activities of glutathione peroxidase, catalase and superoxide dismutase were observed in the plasma of As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>\u2010treated mice; these changes were prevented by pretreatment with resveratrol. In As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>\u2010treated H9c2 cardiomyocytes, resveratrol significantly increased cardiomyocyte viability and attenuated cell apoptosis as measured by acridine orange\/ethidium bromide staining, TdT\u2010mediated dUTP nick end labelling assay and caspase\u20103 activity. As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>\u2010induced generation of ROS and intracellular calcium mobilization in H9c2 cells was also suppressed by pretreatment with resveratrol.<\/jats:p><jats:p><jats:bold>Conclusions and implications:<\/jats:bold> Our results showed that resveratrol significantly attenuated As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>\u2010induced QT prolongation, structural abnormalities and oxidative damage in the heart. In H9c2 cardiomyocytes, resveratrol also decreased apoptosis, production of ROS and intracellular calcium mobilization induced by treatment with As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>. These observations suggested that resveratrol has the potential to protect against cardiotoxicity in As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>\u2010exposed patients.<\/jats:p>","DOI":"10.1038\/bjp.2008.81","type":"journal-article","created":{"date-parts":[[2008,3,10]],"date-time":"2008-03-10T12:38:21Z","timestamp":1205152701000},"page":"105-113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["Resveratrol protects against arsenic trioxide\u2010induced cardiotoxicity <i>in vitro<\/i> and <i>in 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