Carbon Monoxide Inhibits the Expression of Proteins Associated with Intestinal Mucosal Pyroptosis in a Rat Model of Sepsis Induced by Cecal Ligation and Puncture.

Abstract

BACKGROUND Carbon monoxide (CO) has anti-inflammatory effects and protects the intestinal mucosal barrier in sepsis. Pyroptosis, or cell death associated with sepsis, is mediated by caspase-1 activation. This study aimed to investigate the role of CO on the expression of proteins associated with intestinal mucosal pyroptosis in a rat model of sepsis induced by cecal ligation and puncture (CLP). MATERIAL AND METHODS The rat model of sepsis was developed using CLP. Male Sprague-Dawley rats (n=120) were divided into six study groups: the sham group (n=20); the CLP group (n=20); the hemin group (treated with ferric chloride and heme) (n=20); the zinc protoporphyrin IX (ZnPPIX) group (n=20); the CO-releasing molecule 2 (CORM-2) group (n=20); and the inactive CORM-2 (iCORM-2) group (n=20). Hemin and CORM-2 were CO donors, and ZnPPIX was a CO inhibitor. In the six groups, the seven-day survival curves, the fluorescein isothiocyanate (FITC)-labeled dextran 4000 Da (FD-4) permeability assay, levels of intestinal pyroptosis proteins caspase-1, caspase-11, and gasdermin D (GSDMD) were measured by confocal fluorescence microscopy. Proinflammatory cytokines interleukin (IL)-18, IL-1ß, and high mobility group box protein 1 (HMGB1) were measured by Western blot and enzyme-linked immunosorbent assay (ELISA). RESULTS CO reduced the mortality rate in rats with sepsis and reduced intestinal mucosal permeability and mucosal damage. CO also reduced the expression levels of IL-18, IL-1ß, and HMGB1, and reduced pyroptosis by preventing the cleavage of caspase-1 and caspase-11. CONCLUSIONS In a rat model of sepsis induced by CLP, CO had a protective role by inhibiting intestinal mucosal pyroptosis.

• Authors: Hongzhou Wang, Shunwen Zhang, Haijun Zhao, Huiyuan Qin, Jie Zhang, Jiangtao Dong, Hui Zhang, Xiaoling Liu, Zhengyong Zhao, Yanheng Zhao, Meng Shao, Fang Wu, Wanjiang Zhang
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 26 Pg. e920668 (Apr 30 2020) ISSN: 1643-3750 [Electronic] United States
• PMID: 32351244 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Tumor Necrosis Factor-alpha
• Carbon Monoxide
• Caspase 1

Topics

• Animals
• Carbon Monoxide (metabolism, pharmacology)
• Caspase 1 (metabolism)
• Cecum
• Cytokines (metabolism)
• Disease Models, Animal
• Intestinal Mucosa (metabolism)
• Intestines (surgery)
• Ligation (methods)
• Male
• Punctures (methods)
• Pyroptosis (drug effects, genetics, physiology)
• Rats
• Rats, Sprague-Dawley
• Sepsis (drug therapy, genetics, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)