Omeprazole increases survival via different mechanisms in two rat models of liver injury

Abstract

Omeprazole (OMZ) is a proton pump inhibitor (PPI) that is used to reduce gastric acid secretion, but little is known about its possible liver protective effects. This study investigated whether OMZ has beneficial effects in rat septic models of lipopolysaccharide (LPS)-induced liver injury after D-galactosamine (GalN) treatment and 70% hepatectomy (PH), and to determine the mechanisms of OMZ in an in vitro model of liver injury. In the in vivo models, the effects of OMZ were examined 1 h before treatment. OMZ increased survival and decreased tumor necrosis factor-alpha, inducible nitric oxide synthase, cytokine-induced neutrophil chemoattractant 1, interleukin (IL)-6, and IL-1β mRNA expression, and increased IL-10 mRNA expression in the livers of both GaIN/LPS- and PH/LPS-treated rats. Necrosis and apoptosis were inhibited by OMZ in GaIN/LPS rats, but OMZ had no effects on necrosis in PH/LPS rats. Primary rat hepatocytes were treated with IL1-β in the presence or absence of OMZ (in vitro model). OMZ inhibited iNOS induction partially through suppression of NF-κB signaling in hepatocytes. Furthermore, OMZ inhibited the induction of several inflammatory mediators, resulting in the prevention of LPS-induced liver injury after GalN liver failure and PH, although OMZ showed different doses and mechanisms in the two models.