{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T07:26:50Z","timestamp":1768634810410,"version":"3.49.0"},"reference-count":42,"publisher":"Canadian Science Publishing","issue":"2","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:p> Fingolimod (FTY720) inhibits Ca<jats:sup>2+<\/jats:sup>-permeable, Mg<jats:sup>2+<\/jats:sup>-sensitive channels called transient receptor potential melastatin 7 (TRPM7), but its effects on Ca<jats:sup>2+<\/jats:sup> paradox (CP) \u2013 induced myocardial damage has not been evaluated. We studied the effect of FTY720 on CP-induced myocardial damage and used other TRPM7 channel inhibitors nordihydroguaiaretic acid (NDGA) and Mg<jats:sup>2+<\/jats:sup> to test if any effect of FTY720 was via TRPM7 inhibition. Langendorff-perfused Wistar rat hearts were treated with FTY720 or NDGA and subjected to a CP protocol consisting of Ca<jats:sup>2+<\/jats:sup> depletion followed by Ca<jats:sup>2+<\/jats:sup> repletion. Hearts of rats pre-treated with MgSO<jats:sub>4<\/jats:sub> were also subjected to CP. Hemodynamic parameters were measured using an intraventricular balloon, and myocardial infarct size was quantified using triphenyltetrazolium chloride stain. TRPM7 proteins in ventricular tissue were detected using immunoblot analysis. FTY720, but not NDGA, decreased CP-induced infarct size. Both FTY720 and NDGA minimized the CP-induced elevation of left ventricular end-diastolic pressure, but only FTY720 ultimately improved ventricular developed pressure. Mg<jats:sup>2+<\/jats:sup> pre-treatment had no effect on CP-induced infarct size, nor hemodynamic parameters during CP, nor the level of TRPM7 protein expression in ventricular tissue. Overall, FTY720 attenuated CP-induced myocardial damage, with potential therapeutic implications on Ca<jats:sup>2+<\/jats:sup>-mediated cardiotoxicity; however, the cardioprotective mechanism of FTY720 seems to be unrelated to TRPM7 channel modulation. <\/jats:p>","DOI":"10.1139\/cjpp-2021-0381","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T21:39:29Z","timestamp":1632519569000},"page":"134-141","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Cardioprotective effect of fingolimod against calcium paradox\u2013induced myocardial injury in the isolated rat heart"],"prefix":"10.1139","volume":"100","author":[{"given":"Fatma","family":"Alatrag","sequence":"first","affiliation":[{"name":"Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory 7925, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Amoni","sequence":"additional","affiliation":[{"name":"Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory 7925, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roisin","family":"Kelly-Laubscher","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, The College of Medicine and Health, University College Cork, Ireland."},{"name":"Department of Biological Sciences, Faculty of Science, University of Cape Town, Rondebosch 7700, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asfree","family":"Gwanyanya","sequence":"additional","affiliation":[{"name":"Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory 7925, Cape Town, South Africa."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-021-09660-3"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.5830\/CVJA-2020-054"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2013-0081"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00802"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2017.06.004"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1177\/1074248416653831"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-015-9355-6"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12612"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C500294200"},{"key":"refg10\/ref10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00946.2010"},{"key":"refg11\/ref11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2012.05683.x"},{"key":"refg12\/ref12","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00098-X"},{"key":"refg13\/ref13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011161"},{"issue":"3","key":"refg14\/ref14","first-page":"187","volume":"18","author":"Durlach J.","year":"2005","journal-title":"Magnes. 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