title: 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 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.
authors.affiliation: Department of Anesthesia, Pain Management and Perioperative Medicine, QEII Health Sciences Centre, Halifax, Nova Scotia, Canada; Department of Pharmacy, East West University, Dhaka, Bangladesh.
authors.forename: Sufia
authors.initials: S
authors.lastname: Islam
authors.affiliation: Department of Anesthesia, Pain Management and Perioperative Medicine, QEII Health Sciences Centre, Halifax, Nova Scotia, Canada; Department of Anesthesiology and Intensive Care Medicine, Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jarosch
authors.affiliation: Department of Anesthesia, Pain Management and Perioperative Medicine, QEII Health Sciences Centre, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Chelation Partners Inc., Halifax, Nova Scotia, Canada.
authors.forename: Maria del Carmen
authors.initials: Mdel C
authors.lastname: Parquet
authors.affiliation: Department of Anesthesia, Pain Management and Perioperative Medicine, QEII Health Sciences Centre, Halifax, Nova Scotia, Canada; Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: James Thomas
authors.initials: JT
authors.lastname: Toguri
authors.affiliation: Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Colp
authors.affiliation: Chelation Partners Inc., Halifax, Nova Scotia, Canada.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Holbein
authors.affiliation: Department of Anesthesia, Pain Management and Perioperative Medicine, QEII Health Sciences Centre, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: chlehmann@dal.ca.
authors.forename: Christian
authors.initials: C
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D058491:Bacterial Load / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D004359:Drug Therapy, Combination; D015378:Imipenem / Q000494:pharmacology / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007502:Iron Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018805:Sepsis / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D007502:Iron Chelating Agents; D015378:Imipenem
keywords: CASP; Inflammation; Iron chelation; Sepsis