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