Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats

• Published in: International journal of molecular sciences Vol. 16; no. 9; pp. 20595 - 20608
• Main Authors: Wang, Peng, Huang, Jian, Li, Yi, Chang, Ruiming, Wu, Haidong, Lin, Jiali, Huang, Zitong
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.08.2015; MDPI
• Subjects: Acute Kidney Injury - etiology; Acute Kidney Injury - metabolism; Acute Kidney Injury - mortality; Acute Kidney Injury - pathology; Acute Kidney Injury - therapy; Animals; Apoptosis; Blood Urea Nitrogen; Carbon monoxide; Carbon Monoxide - administration & dosage; Carrier Proteins - metabolism; Creatinine - blood; Cytokines - blood; Cytokines - metabolism; Disease Models, Animal; Inflammasomes - metabolism; Inflammation Mediators - blood; Inflammation Mediators - metabolism; Inflammatory diseases; Kidney diseases; Male; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Rats; Rodents; Sepsis; Sepsis - complications; carbon monoxide; acute kidney injury; NLRP3 inflammasome; sepsis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms160920595

Carbon monoxide (CO) has shown various physiological effects including anti-inflammatory activity in several diseases, whereas the therapeutic efficacy of CO on sepsis-induced acute kidney injury (AKI) has not been reported as of yet. The purpose of the present study was to explore the effects of exogenous CO on sepsis-induced AKI and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in rats. Male rats were subjected to cecal ligation and puncture (CLP) to induce sepsis and AKI. Exogenous CO delivered from CO-releasing molecule 2 (CORM-2) was used intraperitoneally as intervention after CLP surgery. Therapeutic effects of CORM-2 on sepsis-induced AKI were assessed by measuring serum creatinine (Scr) and blood urea nitrogen (BUN), kidney histology scores, apoptotic cell scores, oxidative stress, levels of cytokines TNF-α and IL-1β, and NLRP3 inflammasome expression. CORM-2 treatment protected against the sepsis-induced AKI as evidenced by reducing serum Scr/BUN levels, apoptotic cells scores, increasing survival rates, and decreasing renal histology scores. Furthermore, treatment with CORM-2 significantly reduced TNF-α and IL-1β levels and oxidative stress. Moreover, CORM-2 treatment significantly decreased NLRP3 inflammasome protein expressions. Our study provided evidence that CORM-2 treatment protected against sepsis-induced AKI and inhibited NLRP3 inflammasome activation, and suggested that CORM-2 could be a potential therapeutic candidate for treating sepsis-induced AKI.