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Tytuł:
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(R)-Ketamine ameliorates lethal inflammatory responses and multi-organ injury in mice induced by cecum ligation and puncture.
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Autorzy:
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Zhang J; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan; Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Ma L; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan; Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430022, PR China.
Hashimoto Y; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan; Department of Respirology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Wan X; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
Shan J; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
Qu Y; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
Hashimoto K; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan. Electronic address: .
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Źródło:
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Life sciences [Life Sci] 2021 Nov 01; Vol. 284, pp. 119882. Date of Electronic Publication: 2021 Aug 10.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
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MeSH Terms:
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Cecum/*pathology
Inflammation/*drug therapy
Inflammation/*pathology
Ketamine/*therapeutic use
Multiple Organ Failure/*drug therapy
Multiple Organ Failure/*pathology
Animals ; Biomarkers/metabolism ; Cytokines/blood ; Disease Models, Animal ; Inflammation/blood ; Inflammation Mediators/blood ; Ketamine/pharmacology ; Ligation ; Lung/metabolism ; Lung/pathology ; Male ; Mice, Inbred C57BL ; Multiple Organ Failure/blood ; Organ Size/drug effects ; Protective Agents/pharmacology ; Protective Agents/therapeutic use ; Punctures ; Sepsis/blood ; Sepsis/drug therapy ; Mice
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Contributed Indexing:
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Keywords: (R)-ketamine; Cecal ligation and puncture; Inflammation; Multi-organ injury; sepsis
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Substance Nomenclature:
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0 (Biomarkers)
0 (Cytokines)
0 (Inflammation Mediators)
0 (Protective Agents)
690G0D6V8H (Ketamine)
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Entry Date(s):
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Date Created: 20210813 Date Completed: 20211005 Latest Revision: 20240226
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Update Code:
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20240226
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DOI:
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10.1016/j.lfs.2021.119882
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PMID:
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34384829
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Aims: Sepsis is a life-threatening organ dysfunction syndrome arising from infection-induced uncontrolled systemic inflammatory responses. Patients surviving severe sepsis also exhibit increased mortality due to enhanced vulnerability to infections. In this study, we examined whether (R)-ketamine could prevent against lethal sepsis-induced systemic inflammation and inflammatory organ injury.
Main Methods: Septic model was induced by cecal ligation and puncture (CLP) surgery on adult mice. (R)-ketamine (10 or 15 mg/kg) was administrated intraperitoneally (i.p.) 24 h before and/or immediately after CLP.
Key Findings: Combined prophylactic and therapeutic use of (R)-ketamine (10 mg/kg), as well as either prophylactic or therapeutic use of (R)-ketamine at a single dose of 15 mg/kg did not reduce 14-day mortality after CLP. However, combined prophylactic and therapeutic use of (R)-ketamine (15 mg/kg) significantly increased 14-day survival rate, attenuated sepsis-induced marked drop in the rectal temperature and increase in the plasma levels of inflammatory cytokines [i.e., interleukin (IL)-6, IL-17A, tumor necrosis factor (TNF)-α, IL-1β, and IL-10] 12 h after CLP. Furthermore, (R)-ketamine alleviated sepsis-induced increase in the organ injury markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), myocardial kinase (CK-MB), and creatinine 24 h after CLP. Moreover, the increased lung wet/dry weight ratio, pulmonary morphological injury and the pulmonary levels of inflammatory cytokines were also attenuated by (R)-ketamine.
Significance: Combined prophylactic and therapeutic use of (R)-ketamine could attenuate systemic inflammation and inflammatory multi-organ injury in mice after CLP-induced lethal sepsis. Therefore, (R)-ketamine would be a potential prophylactic and therapeutic drug for patients prone to sepsis.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
