HO-1 mediates the effects of HBO pretreatment against sepsis.
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.


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.
Chang
Kuan-Yu
KY
Department of Orthopedics, Mackay Memorial Hospital, Taipei, Taiwan.
Tsai
Pei-Shan
PS
Huang
Te-Yang
TY
Wang
Tao-Yeuan
TY
Yang
Stone
S
Huang
Chun-Jen
CJ
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure; D004790:Enzyme Induction; D006339:Heart Rate; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D006931:Hyperbaric Oxygenation; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008107:Liver Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009504:Neutrophils / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000150:complications / Q000378:metabolism* / Q000628:therapy*
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D008315:Malondialdehyde; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C105245:heme oxygenase-2