Evaluation of the Effects of Empagliflozin on Acute Lung Injury in Rat Intestinal Ischemia-Reperfusion Model

Background: Empagliflozin is a selective sodium-glucose co-transporter (SGLT2) inhibitor that is accepted for the treatment of type 2 diabetes. Positive effects of empagliflozin on systems other than diabetes have been detected. The aim of this study is to evaluate the role of empagliflozin on acute lung injury induced by intestinal ischemia/ reperfusion (I/R). Materials: and methods: A total of 27 male Wistar albino rats were divided into 3 groups: sham, I/R, and I/R+ empagliflozin; each group contains 9 animals. Sham group animals underwent laparotomy without I/R injury. After I/R groups animals underwent laparotomy, 1 h of superior mesenteric artery ligation was followed by 2 h of reperfusion. In the empagliflozin group, 7 days before I/R, empagliflozin (30 mg/kg) was administered by gastric gavage. All animals were killed at the end of reperfusion and lung tissue samples were obtained for immunohistochemical staining and histopathological investigation in all groups. Results: : Serum glucose, AST, ALT, creatinine, native thiol, total thiol, and disulfide levels and disulfide–native thiol, disulfide–total thiol, and native thiol–total thiol ratios as well as the IMA levels were analyzed and compared among the groups. While intestinal I/R significantly increases serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine levels; Thiol/Disulfide did not cause any change in homeostasis parameters and IMA level. Empagliflozin treatment had no significant effect on biochemical parameters. Empagliflozin treatment induced a significant decrease in positive immunostaining for IL-1, IL-6, TNF-alpha, caspase 3, caspase 8, and caspase 9 compared to the I/R group in lung tissue samples. Intestinal I/R caused severe histopathological injury including edema, hemorrhage, increased thickness of the alveolar wall, and infiltration of inflammatory cells into alveolar spaces. Empagliflozin treatment significantly attenuated the severity of intestinal I/R injury. Conclusions: : It was concluded that empagliflozin treatment may have beneficial effects in acute lung injury, and therefore has potential for clinical use Keywords: empagliflozin, intestinal ischemia/ reperfusion, acute lung injury, anti-inflammatory