Anti-inflammatory and anti-bacterial effects of iron chelation in experimental sepsis

Abstract Background Sepsis is the systemic inflammatory response to an infection. Generation of reactive oxygen species represents an important part of the inflammatory cascade in sepsis. Dysregulation of iron homeostasis can further promote the generation of radicals and amplify the damage caused b...

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Published in:The Journal of surgical research 2016-01, Vol.200 (1), p.266-273
Main Authors: Islam, Sufia, PhD, Jarosch, Stefan, DEAA, Zhou, Juan, MD, PhD, Parquet, Maria del Carmen, PhD, Toguri, James Thomas, BSc, Colp, Patricia, Holbein, Bruce E., PhD, Lehmann, Christian, MD, PhD, FRCPC
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Bacterial Load - drug effects
Capillaries - drug effects
Capillaries - physiology
CASP
Cell Adhesion - drug effects
Drug Therapy, Combination
Imipenem - pharmacology
Imipenem - therapeutic use
Inflammation
Injections, Intraperitoneal
Iron Chelating Agents - pharmacology
Iron Chelating Agents - therapeutic use
Iron chelation
Leukocytes - drug effects
Leukocytes - physiology
Male
Mice
Mice, Inbred C57BL
Sepsis
Sepsis - drug therapy
Surgery
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Summary:Abstract Background Sepsis is the systemic inflammatory response to an infection. Generation of reactive oxygen species represents an important part of the inflammatory cascade in sepsis. Dysregulation of iron homeostasis can further promote the generation of radicals and amplify the damage caused by systemic immune activation. This can potentially be suppressed or prevented by iron chelation. Therefore, this study was designed to examine the effects of a novel iron chelator (DIBI) with or without standard antibiotic treatment in colon ascendens stent peritonitis (CASP)-induced experimental sepsis. Methods Six groups of animals (n = 7–10) were included in the study: sham surgery; untreated CASP animals; CASP and subcutaneous (sc) or intraperitoneal DIBI administration, respectively; CASP and imipenem sc; and combination of DIBI and imipenem sc. Results We observed a 55% reduction in leukocyte adhesion in V1 venules after sc administration of DIBI and a 40% reduction after imipenem treatment, when compared to untreated CASP animals ( P  
ISSN:0022-4804
1095-8673
DOI:10.1016/j.jss.2015.07.001