Protective effects of KML29 in intestinal ischemia-reperfusion injury: An experimental study.

Abstract

Background: Acute mesenteric ischemia (AMI) is a potentially fatal vascular emergency that results in tissue damage due to ischemia-reperfusion injury (IRI) and is difficult to diagnose and treat in its early stages. Monoacylglycerol lipase inhibitors have demonstrated protective effects against ischemia-reperfusion injury due to their antioxidant and anti-inflammatory properties. This study aimed to evaluate the effects of KML29, a potent and selective monoacylglycerol lipase inhibitor, on intestinal IRI.

Methods: Thirty-two female Wistar albino rats were divided into four groups: Group 1 - Sham; Group 2 - Ischemia/Reperfusion (IR); Group 3 - IR + KML29 (2 mg/kg); and Group 4 - IR + KML29 (10 mg/kg). Intestinal ischemia-reperfusion was induced by occluding the superior mesenteric artery for 45 minutes, followed by 60 minutes of reperfusion. KML29 was administered intraperitoneally to Groups 3 and 4 at doses of 2 mg/kg and 10 mg/kg, respectively, 30 minutes prior to surgery. Intestinal IRI was evaluated using histopathological and biochemical parameters.

Results: Treatment with 10 mg/kg KML29 was associated with improved histopathological findings in the IR group (p=0.0001). Elevated levels of nuclear factor kappa B (NF-kB), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and transforming growth factor-beta 1 (TGF-β1) observed in the IR group were significantly reduced following administration of 10 mg/kg KML29 (p=0.0001). Additionally, treatment with both 2 mg/kg and 10 mg/kg doses of KML29 significantly reduced the number of apoptotic cells in the IR group (p=0.0001).

Conclusion: In conclusion, this study demonstrated that treatment with both doses of KML29 (2.5 mg/kg and 10 mg/kg) significantly reduced the number of apoptotic cells and inflammatory markers, and improved histopathological findings in the intestinal tissues of rats subjected to IR. With its anti-inflammatory and anti-apoptotic properties, KML29 may represent a novel therapeutic option for the treatment of mesenteric ischemia.