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

• Published in: The Journal of surgical research Vol. 200; no. 1; pp. 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: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2016
• 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; Iron chelation; Sepsis; Inflammation; CASP
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2015.07.001

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  < 0.05). A further reduction in the number of adherent leukocytes in V1 venules has been observed after combined treatment with DIBI and imipenem (66%). A significant decrease in bacterial count was observed from 2200 (150–64,000) to 100 (1–420) colony forming units per milliliter in blood in the sc DIBI and imipenem combination group ( P  = 0.0065). The bacterial count in the peritoneal lavage fluid was also significantly reduced in the sc imipenem group and the sc DIBI and imipenem combination group ( P  = 0.0021 and P  = 0.0001, respectively) when compared to untreated CASP animals. Conclusions These findings suggest a potential role of iron chelators in the treatment of sepsis.