Empagliflozin restores electrocontractile function in cardiomyocytes following tebuconazole exposure
Abstract
AIMS: Tebuconazole (TEB) is a fungicide that has been increasingly associated with cardiovascular effects. The Sodium-Glucose Cotransporter-2 Inhibitors, as Empagliflozin (EMPA), have emerged as a therapeutic class with direct, independent, cardioprotective properties that extend beyond glycemic control. However, the mechanisms underlying these protective actions remain incompletely understood, particularly regarding whether EMPA can mitigate cardiotoxicity triggered by toxicants, as TEB. This study aimed to evaluate the potential action of EMPA during TEB exposure.
MATERIALS AND METHODS: Cardiomyocytes from rats were isolated and divided as: control (vehicle), TEB, and TEB + EMPA (acute exposure). Contractility, action potential, calcium dynamics, and oxidative mechanisms were analyzed. Also, experimental structures of human and rat cardiac channels (Nav1.5, Cav1.2, and Kv4.2) were retrieved and used for high-exhaustiveness whole-protein docking of TEB and EMPA structures.
KEY FINDINGS: EMPA prevented the increase in cell contraction induced by TEB. Moreover, EMPA inhibited TEB-induced depolarization of the resting membrane potential and action potential prolongation. TEB markedly impaired calcium handling in cardiomyocytes, rising transient amplitude and changing kinetics, whereas EMPA attenuated these disturbances. The alterations were not associated with oxidative mechanisms. Docking analyses revealed convergent and state-dependent binding patterns of TEB and EMPA across…
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