Background. Recent meta-analyses have shown that sodium-glucose cotransporter 2 (SGLT-2) inhibitors alleviate chronic kidney disease and acute kidney injury in diabetic patients. In this study, we aimed to investigate the effect of empagliflozin on renal ischemia/reperfusion (I/R) in nondiabetic rats and find the possible mechanisms. Experimental Approach. Eighteen male Wistar rats were randomly divided into three groups, including healthy control, ischemic control, and empagliflozin-treated group. Thirty minutes of bilateral renal ischemia was induced by clamping the renal hilum. Forty-eight hours after reopening the clamps, rats’ blood samples and tissue specimens were collected. Empagliflozin 10 mg/kg was administered by gavage, 2 hours before ischemia and 24 hours after the first dose. Results. I/R injury led to a significant rise in serum creatinine and blood urea nitrogen which was significantly decreased after treatment with empagliflozin. Empagliflozin also alleviated tubulointerstitial and glomerular damage and significantly decreased tissue histology scores. Empagliflozin decreased the increased levels of malondialdehyde, interleukin 1β, and tumor necrosis factor α. SGLT2 inhibition increased the decreased expression of nuclear factor erythroid 2-related factor 2 and PPARG coactivator 1 alpha that conduct antioxidant defense and mitochondrial biogenesis, respectively. Furthermore, empagliflozin markedly increased LC3-II/LC3-I and bcl2/bax ratios, showing its beneficial effect on activation of autophagy and inhibition of apoptosis. Despite its effects on diabetic nephropathy, empagliflozin did not activate the Sestrin2/AMP-activated protein kinase pathway in this study. Conclusion. Empagliflozin improved renal I/R injury in nondiabetic rats in this study by promoting autophagy and mitochondrial biogenesis and attenuation of oxidative stress, inflammation, and apoptosis.
Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced in pregnancy by the developing embryo after conception and later by the syncytiotrophoblast to prevent disintegration of the corpus luteum of the ovary. hCG also plays a role in cellular differentiation/proliferation and may activate apoptosis (1). hCG is extensively used as a parenteral fertility medication in lieu of luteinizing hormone.hCG is composed of 244 amino acids with a molecular mass of 36.7 kDa. It is heterodimeric, with a (alpha) and b (beta) subunits creating a small hydrophobic core. The vast majority of the outer amino acids are hydrophilic.hCG has been radiolabeled mostly with 125 I for various applications, such as kinetic studies of hCG conformations (2), thermodynamic analysis of hCG monoclonal antibodies (3), structure-activity studies (4) and placental protein synthesis studies (5). b-Human chorionic gonadotropin (b-hCG) was successively labeled with [ 67 Ga]-gallium chloride after conjugation with freshly prepared diethylenetriaminepentaacetic acid dianhydride (ccDTPA). After solid phase purification of the radiolabeled hormone, high performance liquid chromatography showed radiochemical purity higher than 95 % under optimized conditions (specific activity = 22-23 TBq mM -1 , labeling efficiency 80 %). Preliminary in vivo studies (ID g -1 , %) in male wild-type rats showed marked gonadal uptake of the tracer after 240 minutes in agreement with the biodistribution studies and reported b-hCG receptors. Target to blood ratios were 5.1 and 15.2 after 3 and 24 hours, respectively, while target to muscle ratios were 35 and 40 after 3 and 24 hours, respectively.
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