Hemoglobin provides protection against lethal endotoxemia in rats: the role of heme oxygenase-1. Academic Article uri icon

Overview

MeSH

  • Animals
  • Bronchoalveolar Lavage Fluid
  • Enzyme Induction
  • Enzyme Inhibitors
  • Gene Expression
  • Male
  • Metalloporphyrins
  • Protoporphyrins
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Shock, Septic

MeSH Major

  • Heme Oxygenase (Decyclizing)
  • Hemoglobins
  • Lipopolysaccharides
  • Lung

abstract

  • Heme oxygenase (HO) catalyzes the rate-limiting step in the degradation of heme to bilirubin. HO-1 is highly induced by heme, its major substrate, and nonheme products, including metal ions and hormones. Interest in HO-1 has been stimulated recently by observations that HO-1 is also highly induced in response to oxidative stress in vitro. The physiologic significance of HO-1 induction following oxidant injury in vivo, however, is poorly understood. In a rat model of lipopolysaccharide endotoxin (LPS)-induced lung injury and sepsis, we demonstrate that the lung responds to LPS by expressing high levels of HO-1 mRNA and enzyme activity. We hypothesize that this HO-1 induction could play a critical role in the lung's defense against LPS. Pretreatment of rats with hemoglobin, a potent inducer of HO-1, resulted in HO-1 induction and more importantly provided complete protection against subsequent lethal endotoxemia (100% survival). Tin protoporphyrin, a competitive inhibitor of HO, blocked this protective effect of hemoglobin and rendered the rats more susceptible to a lethal dose of LPS. Taken together, these data strongly implicate HO-1 in playing an important role in the defense against endotoxic shock, with potential therapeutic implications.

publication date

  • November 1995

has subject area

  • Animals
  • Bronchoalveolar Lavage Fluid
  • Enzyme Induction
  • Enzyme Inhibitors
  • Gene Expression
  • Heme Oxygenase (Decyclizing)
  • Hemoglobins
  • Lipopolysaccharides
  • Lung
  • Male
  • Metalloporphyrins
  • Protoporphyrins
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Shock, Septic

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1165/ajrcmb.13.5.7576696

PubMed ID

  • 7576696

Additional Document Info

start page

  • 595

end page

  • 601

volume

  • 13

number

  • 5