Hemoglobin provides protection against lethal endotoxemia in rats: the role of heme oxygenase-1

Am J Respir Cell Mol Biol. 1995 Nov;13(5):595-601. doi: 10.1165/ajrcmb.13.5.7576696.


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 types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Enzyme Induction / drug effects
  • Enzyme Inhibitors / pharmacology
  • Gene Expression / drug effects
  • Heme Oxygenase (Decyclizing) / antagonists & inhibitors
  • Heme Oxygenase (Decyclizing) / physiology*
  • Hemoglobins / therapeutic use*
  • Lipopolysaccharides / toxicity*
  • Lung / enzymology*
  • Male
  • Metalloporphyrins / pharmacology
  • Protoporphyrins / pharmacology
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Shock, Septic / prevention & control


  • Enzyme Inhibitors
  • Hemoglobins
  • Lipopolysaccharides
  • Metalloporphyrins
  • Protoporphyrins
  • RNA, Messenger
  • tin protoporphyrin IX
  • Heme Oxygenase (Decyclizing)