<p>Esomeprazole alleviates the damage to stress ulcer in rats through not only its antisecretory effect but its antioxidant effect by inactivating the p38 MAPK and NF-κB signaling pathways</p>

Abstract

BackgroundStress ulcer is a severe complication in critically ill patients and causes a high mortality. The proton pump inhibitor esomeprazole is widely applied in the treatment of stress ulcers because of its powerful acid suppression ability. However, the mechanism of stress ulcer and the precise gastroprotective effect of esomeprazole in stress ulcer remain unclear.PurposeIn the present study, the rats with water-immersed and restraint (WIR)-induced stress ulcer were used to further elucidate the anti-ulcerogenic capacity of esomeprazole in stress ulcer in addition to its anti-acid secreting ability.Methods and resultsThe rats were randomly divided into 5 groups: control group (NS), water-immersed and restraint group (WIR), high-dose application of esomeprazole plus stress ulcer-induced group (HE+WIR), low-dose application of esomeprazole plus stress ulcer-induced group (LE+WIR), and high-dose application of esomeprazole without stress ulcer-induced group (HE). Our study showed that the pretreatment of esomeprazole alleviated gastric tissue damage in both macroscopic and histopathological manifestations. Pretreatment of esomeprazole elevated the decline in PEG2 level affected by WIR; and it inhibited the secretion of gastric acid, gastrin and pepsin. Moreover, esomeprazole exerted its antioxidant effects by reducing malondialdehyde levels, enhancing the expressions of antioxidant factors like glutathione and superoxide dismutase (SOD) and reducing the compensatory transcriptional elevation of SOD1 gene. Esomeprazole also reduced the levels of MPO (myeloperoxidase), tumor necrosis factor (TNF)-α and interleukin (IL)-1β according to its anti-inflammatory effects. We further explored the possible mechanism of esomeprazole pretreatment on stress ulcer and demonstrated that esomeprazole attenuated the high phosphorylation levels of nuclear factor kappa B (NF-κB) p65 and p38 MAPK, and decreased the NF-κB p65 nuclear translocation induced by WIR related stress ulcer.ConclusionOur study provides some evidence that the esomeprazole pretreatment exerts gastroprotective effects in WIR-induced stress ulcer through not only its antisecretory effect but also its antioxidant effect by inactivating the p38 MAPK and NF-κB signaling pathways.

Chlorella vulgaris Ameliorates Oxidative Stress and Improves the Muscle Regenerative Capacity of Young and Old Sprague-Dawley Rats

“…Therefore, C. vulgaris may improve muscle mass and decrease fat mass through the inactivation of p38 via its antioxidant properties. A previous study reported that esomeprazole, a treatment for stress ulcers, inactivates the p38 MAPK pathway by its antioxidative effect [49].…”

Use of omeprazole, the proton pump inhibitor, as a potential therapy for the capecitabine-induced hand-foot syndrome

“…Omeprazole and esomeprazole, the S-isomer of omeprazole, have been reported to have anti-inflammatory effects. Moreover, some studies have reported esomeprazole to inhibit TNF-α and IL-1β and other inflammatory molecules such as IL-6, vascular cell adhesion molecule-1, and inducible nitric oxide synthase, which may contribute to the skin protective effect of omeprazole 17 , 20 , 22 , 23 .…”

“…The evaluation of the available studies strongly suggests the involvement of inflammation in the development of capecitabine-induced HFS 16 . On the other hand, proton pump inhibitors (PPIs), including omeprazole, are reported to have anti-inflammatory effects in several animal models 17 – 21 . We hypothesized that omeprazole, with its anti-inflammatory properties, may be effective in preventing or treating HFS.…”

Proton pump inhibitors and peptic ulcer management: Antioxidant mechanisms

“…Esomeprazole has also shown to have a gastro-protective role via its antioxidant activity through inhibiting the signalling pathway of NF-B and p38 MAPK. Treatment with esomeprazole also led to increased antioxidant factors expressions such as GSH and SOD and decreased MDA levels and other invasive triggers such as pepsin, gastric acid and ROS-related inflammatory damage 26 .…”