Carbon monoxide and bilirubin: potential therapies for pulmonary/vascular injury and disease. Review uri icon

Overview

MeSH

  • Animals
  • Humans
  • Oxidative Stress
  • Reperfusion Injury

MeSH Major

  • Bilirubin
  • Carbon Monoxide
  • Lung Diseases
  • Vascular Diseases

abstract

  • Heme oxygenase (HO)-1, an inducible, low-molecular-weight stress protein, confers cellular and tissue protection in multiple models of injury and disease, including oxidative or inflammatory lung injury, ischemia/reperfusion (I/R) injuries, and vascular injury/disease. The tissue protection provided by HO-1 potentially relates to the endogenous production of the end products of its enzymatic activity: namely, biliverdin (BV)/bilirubin (BR), carbon monoxide (CO), and iron. Of these, CO and BV/BR show promise as possible therapeutic agents when applied exogenously in models of lung or vascular injury. CO activates intracellular signaling pathways that involve soluble guanylate cyclase and/or p38 mitogen-activated protein kinase. Although toxic at elevated concentrations, low concentrations of CO can confer antiinflammatory, antiapoptotic, antiproliferative, and vasodilatory effects. BV and BR are natural antioxidants that can provide protection against oxidative stress in cell culture and in plasma. Application of BV or BR protects against I/R injury in several organ models. Recent evidence has also demonstrated antiinflammatory and antiproliferative properties of these pigments. To date, evidence has accumulated for salutary effects of CO, BV, and/or BR in lung/vascular injury models, as well as in models of transplant-associated I/R injury. Thus, the exogenous application of HO end products may provide an alternative to pharmacologic or gene therapy approaches to harness the therapeutic potential of HO-1.

publication date

  • February 2007

has subject area

  • Animals
  • Bilirubin
  • Carbon Monoxide
  • Humans
  • Lung Diseases
  • Oxidative Stress
  • Reperfusion Injury
  • Vascular Diseases

Research

keywords

  • Journal Article
  • Review

Identity

Language

  • eng

PubMed Central ID

  • PMC2176112

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2006-0333TR

PubMed ID

  • 16980550

Additional Document Info

start page

  • 175

end page

  • 182

volume

  • 36

number

  • 2