Publications by authors named "Fatma Alatrag"

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Cardioprotective effect of fingolimod against calcium paradox-induced myocardial injury in the isolated rat heart.

Can J Physiol Pharmacol 2021 Sep 24. Epub 2021 Sep 24.

University of Cape Town, Human Biology, 5.14 Anatomy Building, Observatory, Cape Town, South Africa, 7925;

Fingolimod (FTY720) inhibits Ca-permeable, Mg-sensitive channels called transient receptor potential melastatin 7 (TRPM7), but its effects on Ca paradox (CP)-induced myocardial damage have 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 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 depletion followed by Ca repletion. Hearts of rats pre-treated with MgSO 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 pre-treatment had effect neither on CP-induced infarct size, hemodynamic parameters during CP, nor the level TRPM7 protein expression in ventricular tissue. Overall, FTY720 attenuated CP-induced myocardial damage, with potential therapeutic implications on Ca-mediated cardiotoxicity. However, the cardioprotective mechanism of FTY720 seems to be unrelated to TRPM7 channel modulation.
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September 2021