Table 5 Summary of the effects of SGLT-2 inhibitors on cardiac oxidative stress in animal models
Animal species | Model | Drug/dose/route | Major findings | Interpretation | References |
|---|---|---|---|---|---|
SHR/NDmcr-cp (+/+) rats | Prediabetes/metabolic syndrome | 0.03% empagliflozin/diet/10 weeks | ↓ Cardiac superoxide level | Empagliflozin attenuated cardiac oxidative stress in genetic prediabetic metabolic syndrome rats | [57] |
db/db mice | Diabetes/obesity (diastolic dysfunction and LVH) | Empagliflozin (10 mg/kg/days)/PO/5 weeks | ↔ Cardiac nitrotyrosine level ↔ AGEs and RAGEs expressions | Empagliflozin had no effect on myocardial oxidative/nitrosative stress in db/db mice | [59] |
db/db mice | Diabetes/obesity (diastolic dysfunction and LVH) | 0.03% empagliflozin/diet/10 weeks | ↓ Cardiac and aortic superoxide levels | Empagliflozin attenuated cardiovascular oxidative stress in db/db mice | [58] |
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 | ↓ Malondialdehyde level in ischemic area | Dapagliflozin attenuated cardiovascular oxidative stress in pre-diabetic rats with cardiac I/R injury | [64] |
Wistar rats | MI by LAD ligation in rats | Dapagliflozin (0.1 mg/kg/days)/PO/Start after 1-day infarction for 2 days | ↓ Cardiac superoxide and nitrotyrosine levels ↑ STAT3 activation | Dapagliflozin attenuated cardiac oxidative/nitrosative stress and increased RONS-dependent STAT3-mediated pathway in rats with acute stage of MI | [65] |
Wistar rats | Ex vivo Isolated hearts after 3-day infarction by LAD ligation | Dapagliflozin (10 μM)/media/1 h | ↑ STAT3 activation ↑ IL-10 protein level | Dapagliflozin activated RONS-dependent STAT3-mediated pathway independently from its SGLT-2 and glucose lowering effects | [65] |