Anti-inflammatory effects of a novel iron chelator, DIBI, in experimental sepsis

Taylor Thorburn, Maral Aali, Lisanne Kostek, Chloe LeTourneau-Paci, Patricia Colp, Juan Zhou, Bruce Holbein, David Hoskin, Christian Lehmann

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

26 Citas (Scopus)

Resumen

Background: Iron catalyzes the generation of reactive oxygen species (ROS) as part of the innate antimicrobial defense. During sepsis, the dysregulated systemic inflammatory response to infection, iron homeostasis becomes disrupted, generating an excess of ROS causing damage to tissues. This can be potentially suppressed using iron chelators that selectively bind iron to prevent its participation in ROS-related inflammatory reactions. Objective: We hypothesize that administration of DIBI, a novel iron-chelator, attenuates the dysregulated systemic immune response and reduces tissue damage in experimental endotoxemia. Methods: Five groups of animals (n = 5-10) were included in this study: control, untreated endotoxemia, and endotoxemia animals treated with either DIBI-A,MAHMP, or DIBI-B. Intravital microscopywas performed on the intestine of anesthesized mice to observe leukocyte endothelial interactions and evaluate the intestinal microcirculation. Results: Treatment of endotoxemic mice with DIBI-B reduced the number of adhering leukocytes in submucosal collecting (V1) venules by 68%. DIBI-B, MAHMP, and DIBI-A were able to restore functional capillary density (FCD) in the intestinal muscle layer by 74%, 44%, and 11%, respectively. Conclusions: DIBI-B reduces leukocyte recruitment and improves FCD in experimental endotoxemia, outperforming other chelators tested. These findings suggest a potential role for DIBI-B as a candidate drug for sepsis treatment.

Idioma originalEnglish
Páginas (desde-hasta)241-250
Número de páginas10
PublicaciónClinical Hemorheology and Microcirculation
Volumen67
N.º3-4
DOI
EstadoPublished - 2017

Nota bibliográfica

Publisher Copyright:
© 2017 - IOS Press and the authors. All rights reserved.

ASJC Scopus Subject Areas

  • Physiology
  • Hematology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

PubMed: MeSH publication types

  • Journal Article

Huella

Profundice en los temas de investigación de 'Anti-inflammatory effects of a novel iron chelator, DIBI, in experimental sepsis'. En conjunto forman una huella única.

Citar esto