Determination of the biochemical effects of the APJ receptor in the liver in trinitrobenzene sulfonic acid-induced colitis model

The apelinergic system, which plays a role in physiological processes such as inflammation, oxidative stress, and cell proliferation, consists of the APJ receptor and its ligands, apelin and apela. In this study, we investigated the biochemical effects of pharmacological inhibition of the APJ receptor on colonic inflammation, mucosal barrier integrity, and colitis-associated liver injury in a TNBS-induced experimental colitis model. Considering that APJ signaling may have tissue-specific effects, the outcomes of its inhibition were evaluated in both colon and liver tissues. In the study, male Wistar rats were divided into four groups: control, F13A, TNBS, and TNBS + F13A. While the colitis model was induced with TNBS, F13A was used in the inhibition of the APJ receptor. In addition to clinical evaluations, macroscopic, histological, and mucosal barrier parameters were assessed in the colon, while histopathological, inflammatory, and oxidative stress markers were biochemically analyzed in the liver. With F13A, histopathological findings associated with colitis in the colon were alleviated, ZO-1 expression, mucus production and PGE₂ level were increased. In the liver, histopathological and some biochemical parameters improved, no significant amelioration was observed in inflammation and oxidative stress markers. These findings suggest that pharmacological inhibition of the APJ receptor may provide protective effects on colonic barrier function; however, its therapeutic efficacy against hepatic inflammation appears to be limited. Studies based on dose, duration, and route of administration with different ligands or inhibitors may more clearly reveal the tissue-specific effects of the APJ signaling pathway and illuminate the role of the apelinergic system in inflammatory diseases.