Differential Effects of the Apelin Receptor Blockade by [Ala13]-Apelin-13 on Colonic Barrier Integrity and Hepatic Inflammatory Responses in Chemically Induced Colitis

Abstract

The apelin receptor (APJ) is widely expressed throughout the body and plays important roles in the regulation of inflammation, oxidative stress, and tissue repair. Because APJ signaling is highly context dependent and may vary according to tissue type, inflammatory status, and ligand activity, its biological consequences during inflammatory diseases remain incompletely understood. Inflammatory bowel disease (IBD) is associated not only with intestinal inflammation but also with gut–liver axis–related hepatic alterations. The present study investigated the effects of pharmacological APJ blockade with [Ala13]-apelin-13 (F13A) on intestinal barrier integrity and hepatic inflammatory responses in experimental colitis. Male Wistar rats were divided into four groups ( n = 8): control, F13A, TNBS, and TNBS + F13A. Experimental colitis was induced with 2,4,6-trinitrobenzenesulfonic acid (TNBS) (100 mg/kg, i.r.), and F13A (30 µg/kg/day, i.v.) was administered for 3 days following colitis induction. Colonic and hepatic responses were evaluated using clinical, histopathological, biochemical, and immunohistochemical analyses. F13A treatment markedly attenuated the clinical, macroscopic, and histopathological manifestations of colitis while preserving intestinal barrier integrity, as evidenced by increased zonula occludens-1 (ZO-1) expression, mucus production, and prostaglandin E₂ (PGE₂) levels. In contrast, hepatic protection was only partial, with improvements in histopathological injury, myeloperoxidase (MPO) activity, interleukin-10 (IL-10), and PGE₂ levels, whereas tumour necrosis factor-α (TNF-α), lipopolysaccharide (LPS), total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), and apelin levels were not fully restored. These findings suggest that APJ blockade with F13A preserves intestinal barrier integrity while only partially attenuating hepatic inflammatory responses, highlighting tissue-specific effects during experimental colitis. Further studies using alternative APJ-targeting strategies and mechanistic approaches are required to better define the context-dependent role of APJ signaling during intestinal inflammation.