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Table 5 Summary of the effects of SGLT-2 inhibitors on cardiac oxidative stress 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
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]
  1. SGLT-2 sodium–glucose co-transporter 2, LVH left ventricular hypertrophy, PO per oral, AGEs advanced glycation end products, RAGEs receptors for AGEs, I/R ischemic/reperfusion, MI myocardial infarction, LAD left anterior descending artery, STAT3 signal transducer and activator of transcription 3, RONS reactive oxygen and nitrogen species