Cardioprotective effect of fingolimod against calcium paradox–induced myocardial injury in the isolated rat heart
| العنوان: | Cardioprotective effect of fingolimod against calcium paradox–induced myocardial injury in the isolated rat heart |
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| المؤلفون: | Roisin Kelly-Laubscher, Asfree Gwanyanya, Fatma Alatrag, Matthew Amoni |
| المصدر: | Canadian Journal of Physiology and Pharmacology. 100:134-141 |
| بيانات النشر: | Canadian Science Publishing, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Male, Cardiotonic Agents, Physiology, Myocardial Infarction, TRPM7, TRPM Cation Channels, In Vitro Techniques, Pharmacology, Transient receptor potential channel, hemic and lymphatic diseases, Physiology (medical), medicine, Animals, Masoprocol, Magnesium, Rats, Wistar, Fingolimod Hydrochloride, Chemistry, Calcium paradox, Fingolimod, General Medicine, Rat heart, Ion channels, Calcium, Cardiac, medicine.drug |
| الوصف: | Fingolimod (FTY720) inhibits Ca2+-permeable, Mg2+-sensitive channels called transient receptor potential melastatin 7 (TRPM7), but its effects on Ca2+ paradox (CP) – 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 Mg2+ 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 Ca2+ depletion followed by Ca2+ repletion. Hearts of rats pre-treated with MgSO4 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. Mg2+ 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 Ca2+-mediated cardiotoxicity; however, the cardioprotective mechanism of FTY720 seems to be unrelated to TRPM7 channel modulation. |
| وصف الملف: | application/pdf |
| تدمد: | 1205-7541 0008-4212 |
| DOI: | 10.1139/cjpp-2021-0381 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ec891006f41586d1c68d1defe76bdfd2 https://doi.org/10.1139/cjpp-2021-0381 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ec891006f41586d1c68d1defe76bdfd2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 12057541 00084212 |
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| DOI: | 10.1139/cjpp-2021-0381 |