Empagliflozin attenuates transient cerebral ischemia/reperfusion injury in hyperglycemic rats via repressing oxidative–inflammatory–apoptotic pathway

Abstract

Hyperglycemia is one of the ischemic neuronal damage triggers that exacerbate the response to oxidative stress, inflammation, and apoptosis induced by cerebral ischemia/reperfusion (I/R) injury. Empagliflozin, a sodium–glucose cotransporter 2 (SGLT 2) inhibitor, was shown to effectively reduce hyperglycemia and glucotoxicity besides improving glycemic control in diabetics. Therefore, the present study was conducted to investigate the neuroprotective effect of empagliflozin against cerebral I/R injury in hyperglycemic rats. Hyperglycemia was induced by streptozotocin (55 mg/kg), and transient cerebral I/R was induced by bilateral common carotid occlusion for 30 min followed by 24‐h reperfusion. Either empagliflozin (10 mg/kg; i.p.) or gliclazide (2 mg/kg, p.o.) was administered at 1 and 24 h after reperfusion. Treatment with empagliflozin showed a significant amelioration of behavioral/neurological functions and histopathological changes observed in brain tissues of hyperglycemic rats subjected to cerebral I/R injury. Comparable to gliclazide, empagliflozin decreased cerebral infarct volume along with suppression of cerebral oxidative stress, inflammatory, and apoptotic markers in brain tissues of hyperglycemic I/R‐injured rats. These findings suggested that empagliflozin can significantly alleviate neuronal damage resulting from global I/R injury induced in hyperglycemic rats. The proposed neuroprotective effect of empagliflozin may be attributed to its glycemic control effect and related antioxidant, anti‐inflammatory, and antiapoptotic effects.

COVID-19 and diabetes management: What should be considered?

“…The effect of reducing the inflammatory stress and the peripheral insulin resistance by lowering the infiltrate with macrophage, via GLP-1 dependent signaling by regulating M1/M2 macrophage polarization, have been described with DPP4 inhibition and GLP-1 activation [16]. Similar evidence on the effect on inflammation is also available for the SGLT-2i [17] and pioglitazone [18]. Therefore, waiting for specific clinical data, certainly it is the case to balance between the potential dangerous effects of some drugs, supported mainly by experimental data, and the proven effects of the drugs on the cardiovascular system and the kidney, as well as their potential anti-inflammatory action.…”

The COVID-19 pandemic and diabetes mellitus

“…Regarding the newer antidiabetic agents, GLP-1 receptor analogues have shown significant anti-inflammatory and anti-adipogenic effects [ 53 , 54 ], but no data exist regarding their effect on patients with COVID-19. Similar evidence on the effect on inflammation is also available for the sodium-glucose cotransporter-2 (SGLT-2) inhibitors [ 55 ]. However, SGLT-2 inhibitors should be used with caution in patients with COVID-19 since there is the fear of euglycemic diabetic ketoacidosis in case of dehydration.…”

COVID-19 and the World with Co-Morbidities of Heart Disease, Hypertension and Diabetes

“…Though the utility of GLP-1Ra and SGLT-2i in such conditions may be well known but under co-morbid situations with COVID-19 their role in preserving cardiovascular and renal function need to be evaluated 92,93 . Some of them may have beneficial effects on oxidative-inflammatoryapoptotic pathway thus preventing oxidative stress, inflammation and apoptosis thereby attenuating vascular ischemia/reperfusion injury 94 . Another mechanism for increased severity and mortality is believed to be increased susceptibility of the COVID-19 co-morbid patients to infections of microbial pathogens including bacteria and fungi 95-97 .…”