Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats.
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.
Department of Emergency Medicine, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China. pengwangsysu@foxmail.com.|Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou 510120, China. pengwangsysu@foxmail.com.
Peng
P
Wang
Department of Nephrology, the Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China. hj510182@126.com.
Jian
J
Huang
Department of Emergency Medicine, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China. doctorli113@163.com.|Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou 510120, China. doctorli113@163.com.
Yi
Y
Li
Department of Emergency Medicine, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China. rubby866@126.com.
Ruiming
R
Chang
Department of Emergency Medicine, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China. wywhd@163.com.
Haidong
H
Wu
Department of Emergency Medicine, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China. cheatl@163.com.|Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou 510120, China. cheatl@163.com.
Jiali
J
Lin
Department of Emergency Medicine, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China. huangzt@mail.sysu.edu.cn.|Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou 510120, China. huangzt@mail.sysu.edu.cn.
Zitong
Z
Huang
D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000818:Animals; D017209:Apoptosis; D001806:Blood Urea Nitrogen; D002248:Carbon Monoxide / Q000008:administration & dosage*; D002352:Carrier Proteins / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D058847:Inflammasomes / Q000378:metabolism*; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress; D051381:Rats; D018805:Sepsis / Q000150:complications*
D002352:Carrier Proteins; D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D002248:Carbon Monoxide; D003404:Creatinine
NLRP3 inflammasome; acute kidney injury; carbon monoxide; sepsis