Early administration of empagliflozin preserved heart function in cardiorenal syndrome in rat
Abstract
This study tested the hypothesis that early administration of empagliflozin (Empa), an inhibitor of glucose recycling in renal tubules, could preserve heart function in cardiorenal syndrome (CRS) in rat. Chronic kidney disease (CKD) was caused by 5/6 subtotal nephrectomy and dilated cardiomyopathy (DCM) by doxorubicin (DOX) treatment. In vitro results showed that protein expressions of cleaved-caspase3 and autophagy activity at 24 h/48 h in NRK-52P cells were significantly upregulated by para-Creso treatment; these were significantly downregulated by Empa treatment. Flow cytometric analysis showed that annexin-V (i.e., early/late apoptosis) in NRK-52P cells expressed an identical pattern to cleaved-caspase3 between the two groups (all p < 0.001). Adult-male-SD rats (n = 18) were equally categorized into group 1 (sham-control), group 2 (CRS) and group 3 [CRS + Empa; 20 mg/kg/day]. By day-42 after CRS induction, left-ventricular ejection fraction (LVEF) level exhibited an opposite pattern, whereas LV end-diastolic dimension and creatinine level displayed the same pattern, to cleaved-caspase3 among the three groups (all p < 0.0001). In LV tissues, protein expressions of inflammatory (tumor-necrosis factor-α/nuclear-factor-κB/interleukin-1ß/matrix-metalloprotianse-9), oxidative stress (NOX-1/NOX-2/oxidized protein), apoptotic (mitochondrial-Bax/cleaved-caspase-3/cleaved-PARP), fibrotic (transforming-growth factor-ß/Smad3), DNA/mitochondrial-damage (γ-H2AX/cytosolic-cytochrome-C)…
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