Heme oxygenase-1/carbon monoxide: novel therapeutic strategies in critical care medicine. Review uri icon

Overview

MeSH

  • Animals
  • Drug Design
  • Enzyme Induction
  • Humans
  • Sepsis

MeSH Major

  • Acute Lung Injury
  • Anti-Inflammatory Agents, Non-Steroidal
  • Carbon Monoxide
  • Heme Oxygenase-1
  • Respiratory Distress Syndrome, Adult

abstract

  • Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remain major causes of morbidity and mortality in critical care medicine despite advances in therapeutic modalities. ALI can be associated with sepsis, trauma, pharmaceutical or xenobiotic exposures, high oxygen therapy (hyperoxia) and mechanical ventilation. The stress protein heme oxygenase-1 (HO-1) provides an inducible defense mechanism that can protect lung cells and tissues against injury. HO-1 degrades heme to biliverdin-IXalpha, carbon monoxide (CO), and iron. Each of these reaction products has been implicated in the cytoprotection associated with HO-1 expression. At low concentrations, CO can confer cyto-protective and tissue-protective effects involving the inhibition of inflammatory, proliferative, and apoptotic signaling. Lung protection by HO-1 has been demonstrated in vitro and in vivo in several models of experimental ALI and sepsis. Recent studies have also explored the protective effects of pharmacological or inhalation CO therapy in animal models of ALI/sepsis. CO has shown therapeutic potential in models of oxidative and acid-induced lung injury, ventilator-induced lung injury, endotoxin challenge, and cecal-ligation and puncture induced-sepsis. Despite therapeutic benefit in animal model studies, the efficacy of CO in humans with these conditions remains unclear, and awaits further controlled clinical studies. This review will summarize recent findings on the therapeutic applications of HO-1 and its end-product CO in the lung, with an emphasis on lung injury models relevant to critical care medicine.

publication date

  • December 2010

has subject area

  • Acute Lung Injury
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal
  • Carbon Monoxide
  • Drug Design
  • Enzyme Induction
  • Heme Oxygenase-1
  • Humans
  • Respiratory Distress Syndrome, Adult
  • Sepsis

Research

keywords

  • Journal Article
  • Review

Identity

Language

  • eng

PubMed ID

  • 20704552

Additional Document Info

start page

  • 1485

end page

  • 1494

volume

  • 11

number

  • 12