HO-1 mediates the effects of HBO pretreatment against sepsis

J Surg Res. 2006 Nov;136(1):143-53. doi: 10.1016/j.jss.2006.06.004. Epub 2006 Aug 23.


Background: We have recently shown that attenuation of sepsis-induced lung injury by hyperbaric oxygen (HBO) pretreatment involves expression regulation of inducible nitric oxide synthase (iNOS) and heme oxygenase (HO)-1. This study was performed to determine the effects of HBO pretreatment on acute kidney and liver injuries in septic rats and the roles of iNOS and HO-1.

Materials and methods: One group of adult male rats (n = 48) were pretreated with HBO. The other group of rats (n = 48) breathed air at normal atmospheric pressure instead. Rats in each group were randomly allocated to receive injection of lipopolysaccharide (LPS), normal saline (N/S), LPS plus hemin (a HO-1 inducer), hemin, LPS plus SnPP (a HO-1 inhibitor), SnPP, LPS plus hemin plus SnPP, or hemin plus SnPP. Hemin and SnPP were injected at 1 h before HBO or air pretreatment. Rats were maintained for 6 h before sacrifice.

Results: LPS caused prominent kidney and liver injuries as well as iNOS and HO-1 expression in stimulated rats. HBO pretreatment significantly attenuated LPS-induced kidney but not liver injury. However, in conjunction with hemin (a HO-1 inducer), HBO pretreatment did attenuate LPS-induced liver injury. In addition, the inhibition of iNOS expression by HBO pretreatment was associated with "super-induction" (i.e., further enhancement) of LPS-induced HO-1 expression. Furthermore, the therapeutic effect of HBO could be counteracted by SnPP (a HO-1 inhibitor).

Conclusions: HBO pretreatment significantly attenuates LPS-induced acute organ injuries in septic rats. The beneficial effect of HBO pretreatment against sepsis is mediated, at least in part, by "super-induction" of HO-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Blood Pressure
  • Enzyme Induction
  • Heart Rate
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Hyperbaric Oxygenation*
  • Kidney Diseases / etiology
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control*
  • Lipopolysaccharides / pharmacology
  • Liver Diseases / etiology
  • Liver Diseases / pathology
  • Liver Diseases / prevention & control*
  • Male
  • Malondialdehyde / metabolism
  • Neutrophils / pathology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Peroxidase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sepsis / complications
  • Sepsis / metabolism*
  • Sepsis / therapy*


  • Lipopolysaccharides
  • Nitric Oxide
  • Malondialdehyde
  • Peroxidase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • heme oxygenase-2