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The caspase-1 Inhibitor AC-YVAD-CMK Attenuates Acute Gastric Injury in Mice: Involvement of Silencing NLRP3 Inflammasome Activities

The caspase-1 Inhibitor AC-YVAD-CMK Attenuates Acute Gastric Injury in Mice: Involvement of Silencing NLRP3 Inflammasome Activities

Fang Zhang, Liang Wang, Jun-Jie Wang, Peng-Fei Luo, Xing-Tong Wang, Zhao-Fan Xia

Sci Rep. 2016 Apr 7;6:24166.

PMID: 27053298

Abstract:

This study evaluated the protective effects of inhibiting caspase-1 activity or gastric acid secretion on acute gastric injury in mice. AC-YVAD-CMK, omeprazole, or vehicle were administered to mice before cold-restraint stress- or ethanol-induced gastric injury. Survival rates and histological evidence of gastric injury of mice pretreated with AC-YVAD-CMK or omeprazole, and exposed to cold-restraint stress, improved significantly relative to the vehicle group. The increased levels of tumour necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-18 following cold-stress injury were decreased by AC-YVAD-CMK, but not omeprazole, pretreatment. The increased expression of CD68 in gastric tissues was inhibited significantly by AC-YVAD-CMK pretreatment. Inhibiting caspase-1 activity in the NLRP3 inflammasome decreased gastric cell apoptosis, and the expression of Bax and cleaved caspase-3. AC-YVAD-CMK pretreatment significantly inhibited cold-restraint stress-induced increases in the expression of phosphorylated IκB-alpha and P38. General anatomy and histological results showed the protective effect of AC-YVAD-CMK on ethanol-induced acute gastric injury. Overall, our results showed that the caspase-1 inhibitor AC-YVAD-CMK protected against acute gastric injury in mice by affecting the NLRP3 inflammasome and attenuating inflammatory processes and apoptosis. This was similar to the mechanism associated with NF-κB and P38 mitogen-activated protein kinase signalling pathways.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP178603786-A	Ac-YVAD-cmk		178603-78-6	Price

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