Imeglimin confers protection against intestinal ischemia/reperfusion injury in rats through AMPK-dependent inhibition of NF-κB/NLRP3 inflammasome signaling and mitigation of oxidative stress and apoptosis

Abstract

Intestinal ischemia/reperfusion (I/R) injury is a critical condition characterized by oxidative stress, inflammation, and apoptosis, leading to significant tissue damage. Imeglimin (IMEG), a novel antidiabetic agent, has recently shown cytoprotective effects through modulation of mitochondrial function, oxidative stress, and inflammatory pathways. We aimed to investigate the potential protective effects of IMEG against II/R injury and to explore the underlying mechanisms involved. Thirty-two adult male Wistar albino rats were divided into four groups; sham group, IMEG group, intestinal I/R group, IMEG + Intestinal I/R group. Oxidative stress markers [malondialdehyde (MDA), reduced glutathione (GSH)], and histopathological changes were assessed. Biochemical analyses included measurement of phosphorylated AMP-activated protein kinase (p-AMPK), NOD-like receptor protein 3 (NLRP3) and caspase-3. Also, gene expression of interleukin (IL)-1β, caspase-1, apoptotic Bcl-2-associated protein x (BAX) and anti-apoptotic B-cell leukemia/lymphoma 2 protein (Bcl-2) were measured. Nuclear factor-κB (NF-κB) immuno expression was estimated. MDA, NLRP3, caspase-3 levels, IL-1β, caspase-1, Bax gene expression, and NF-κB immunohistochemical expression were all significantly elevated in the intestinal I/R group while GSH, p-AMPK levels and Bcl-2 gene expression were significantly decreased. Every metric indicated a notable improvement with IMEG. IMEG exerts a protective effect against intestinal I/R injury through its antioxidant, anti-inflammatory, and anti-apoptotic properties (Fig. 1).