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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

Authors Xie W, Huang X, Chen R, Chen R, Li T, Wu W, Huang Z

Received 6 November 2018

Accepted for publication 16 May 2019

Published 22 August 2019 Volume 2019:13 Pages 2969—2984

DOI https://doi.org/10.2147/DDDT.S193641

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Georgios D. Panos


Wei Xie,*,1 Xielin Huang,*,2 Renpin Chen,1 Ruru Chen,1 Tang Li,1 Wei Wu,1 Zhiming Huang1

1Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
 
*These authors contributed equally to this work

Correspondence: Wei Wu; Zhiming Huang
Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Wenzhou 325000, People’s Republic of China
Tel +86 135 6629 0340
Fax +86 137 0665 8620
Email wwwwwuwei@126.com; wyyyhzhiming@126.com


Background: Stress 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.
Purpose: In 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 results: The 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.
Conclusion: Our 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.

Keywords: stress ulcer, esomeprazole, oxidative stress, NF-κB, MAPK-p38

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