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Table 6 Summary of the effects of SGLT-2 inhibitors on cardiac apoptosis in animal models

From: Potential mechanisms responsible for cardioprotective effects of sodium–glucose co-transporter 2 inhibitors

Animal species Model Drug/dose/route Major findings Interpretation References
Wistar rats Streptozotocin-induced diabetic cardiomyopathy Empagliflozin (30 or 10 mg/kg/days)/PO/8 weeks ↓ Apoptotic cells
↓ GRP78, CHOP protein expression
↓ Caspase-12 activity
↓ ATF4, TRAF2, and XBP1 mRNA
All effects are in dose-dependent manner
Empagliflozin, in dose-dependent manner, attenuated cardiomyocyte apoptosis by suppressing the endoplasmic reticulum stress pathway in streptozotocin-induced diabetic cardiomyopathy rats [62]
ob/ob mice T2DM/obesity (LV diastolic dysfunctions) Empagliflozin (10 mg/kg/days)/PO/6 weeks ↔ Bcl2 and Bax levels Empagliflozin had no effect on apoptotic protein expressions in ob/ob mice [60]
BTBR ob/ob mice T2DM Dapagliflozin (1 mg/kg/days)/PO/8 weeks ↓ Apoptotic cells Dapagliflozin attenuated cardiomyocyte apoptosis in BTBR ob/ob mice [63]
Rats High fat diet induced obese-insulin resistance for 4 weeks then I/R injury by LAD ligation Dapagliflozin (1 mg/kg/days)/PO/4 weeks ↓ Bax/Bcl-2 ratio
↓ Cleavage caspase 3 level
Dapagliflozin attenuated apoptotic protein expressions in pre-diabetic rats with cardiac I/R injury [64]
  1. SGLT-2 sodium–glucose co-transporter 2, PO per oral, GRP78 glucose-regulated protein 78, CHOP CCAAT-enhancer-binding protein homologous protein, ATF4 activating transcription factor 4, TRAF2 tumor necrosis factor receptor-associated factor 2, XBP1 X-box binding protein 1, T2DM type 2 diabetic mellitus, LV left ventricular, Bcl-2 B-cell chronic lymphocytic leukemia/lymphoma-2, Bax Bcl-2-associated X, I/R ischemic/reperfusion, LAD left anterior descending artery