Aprepitant alleviates acute lung injury in a rat model of hepatic ischemia-reperfusion via NLRP3/IL-1β signaling pathway.

Hepatic ischemia reperfusion (HIR) injury is a complication that complicates major liver surgeries and contributes to significant hepatic and remote organs damage. Aprepitant (Ap), a neurokinin-1 receptor (NK-1R) antagonists, is an antiemetic commonly used in preventing chemotherapy-induced nausea and vomiting. This study aimed to evaluate the potential protective effect of Ap against acute lung injury (ALI) associated with HIR, utilizing the Pringle maneuver to induce 30 min of hepatic ischemia followed by 1 h of reperfusion, while targeting the NLRP3/IL-1β signaling pathway. Serum alanine transaminase (ALT), aspartate transaminase (AST), Lung malondialdehyde (MDA), total antioxidant capacity (TAC), reduced glutathione (GSH), tumor necrosis factor-alpha (TNF-α), caspase-3 levels, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome, cleaved caspase-3 expressions were evaluated. Hepatic and lung specimens were evaluated histopathologically and an immunohistochemical study of lung interlukin 1beta (IL-1β) was also performed. HIR caused hepatic and lung damage as shown histopathologically and by an increase in serum ALT, AST and lung IL-1β. A significant increase in lung MDA, TNF-α, caspase-3 levels, NLRP3 and cleaved caspase-3 expressions and decrease in TAC and GSH parameters were detected. Ap significantly ameliorated the oxidative stress, inflammatory, and apoptotic parameters, and this was accompanied by a significant improvement in the histopathological findings with reduction in lung IL-1β. Targeting the NLRP3/IL-1β signaling pathway, as shown by Ap in our murine model, could reveal a promising therapeutic approach to protect against ALI during major liver surgeries.