Journal article
A novel pH-controlled hydrogen sulfide donor protects gastric mucosa from aspirin-induced injury
Journal of cellular and molecular medicine, Vol.21(10), pp.2441-2451
10/2017
Handle:
https://hdl.handle.net/2376/108676
PMCID: PMC5618702
PMID: 28387464
Abstract
Hydrogen sulphide (H
S) serves as a vital gastric mucosal defence under acid condition. Non-steroidal anti-inflammatory drugs (NSAIDs) are among widely prescribed medications with effects of antipyresis, analgesia and anti-inflammation. However, their inappropriate use causes gastric lesions and endogenous H
S deficiency. In this work, we reported the roles of a novel pH-controlled H
S donor (JK-1) in NSAID-related gastric lesions. We found that JK-1 could release H
S under mild acidic pH and increase solution pH value. Intragastrical administration of aspirin (ASP), one of NSAIDs, to mice elicited significant gastric lesions, evidenced by mucosal festering and bleeding. It also led to infiltration of inflammatory cells and resultant releases of IL-6 and TNF-α, as well as oxidative injury including myeloperoxidase (MPO) induction and GSH depletion. In addition, the ASP administration statistically inhibited H
S generation in gastric mucosa, while up-regulated cyclooxygenase (COX)-2 and cystathionine gamma lyase (CSE) expression. Importantly, these adverse effects of ASP were prevented by the intragastrical pre-administration of JK-1. However, JK-1 alone did not markedly alter the property of mouse stomachs. Furthermore, in vitro cellular experiments showed the exposure of gastric mucosal epithelial (GES-1) cells to HClO, imitating MPO-driven oxidative injury, decreased cell viability, increased apoptotic rate and damaged mitochondrial membrane potential, which were reversed by pre-treatment with JK-1. In conclusion, JK-1 was proved to be an acid-sensitive H
S donor and could attenuate ASP-related gastric lesions through reconstruction of endogenous gastric defence. This work indicates the possible treatment of adverse effects of NSAIDs with pH-controlled H
S donors in the future.
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Details
- Title
- A novel pH-controlled hydrogen sulfide donor protects gastric mucosa from aspirin-induced injury
- Creators
- Chun-Tao Yang - Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, ChinaZhen-Zhen Lai - NanShan School of the First Clinical College, Guangzhou Medical University, Guangzhou, 510120, ChinaZe-Hang Zheng - Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, ChinaJian-Ming Kang - Department of Chemistry, Washington State University, Pullman, WA, USAMing Xian - Department of Chemistry, Washington State University, Pullman, WA, USARui-Yu Wang - Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, ChinaKun Shi - Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, ChinaFu-Hui Meng - Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, ChinaXiang Li - Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, ChinaLi Chen - Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, ChinaHui Zhang - Quality Control Section of Academic Affairs, Guangzhou Medical University, Guangzhou, China
- Publication Details
- Journal of cellular and molecular medicine, Vol.21(10), pp.2441-2451
- Academic Unit
- Chemistry, Department of; Pharmaceutical Sciences, Department of
- Publisher
- England
- Grant note
- R01 HL116571 / NHLBI NIH HHS
- Identifiers
- 99900547359801842
- Language
- English
- Resource Type
- Journal article