Induction of heme-oxygenase-1 prevents the systemic responses to hemorrhagic shock.
Oxidant-mediated reperfusion injury of the gut is a major contributor of the systemic inflammatory response in hemorrhagic shock. Recent studies have suggested that heme-oxygenase-1 (HO-1) represents an endogenous protective mechanism against oxidant stress. We assessed whether HO-1 induction modulates the synthesis of tumor necrosis factor-alpha (TNF-alpha) in hemorrhagic shock. In rats submitted to hemorrhagic shock, pretreatment with hemoglobin (Hb) increased HO-1 mRNA expression in macrophages. This increased expression was associated with a decreased expression of TNF-alpha mRNA, as well as decreased plasma concentrations of TNF-alpha. These effects of Hb were reduced by the HO-1 inhibitor tin-protoporphyrin (Sn-PP 20 micromol/kg), while Sn-PP had no effect in the absence of Hb. In parallel, Hb pretreatment reduced pulmonary edema, vascular injury, and increased mesenteric blood flow, and these effects were reduced by Sn-PP. Thus, induction of HO-1 is protective in hemorrhagic shock, possibly through its antioxidant properties. Interventions that induce HO-1 may be beneficial in the treatment of shock states, leading to a reduced systemic inflammatory response.
Tamion
F
F
INSERM E9920, IFRMP and Service de Réanimation Médicale, Rouen University Hospital, France. fabienne.tamion@chu-rouen.fr
Richard
V
V
Bonmarchand
G
G
Leroy
J
J
Lebreton
J P
JP
Thuillez
C
C
D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005440:Fluid Therapy / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology* / Q000627:therapeutic use*; D006439:Hemodynamics; D007249:Inflammation; D007422:Intestines / Q000098:blood supply*; D017737:Macrophages, Peritoneal / Q000201:enzymology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications*; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000201:enzymology* / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D013152:Splanchnic Circulation / Q000502:physiology; D018746:Systemic Inflammatory Response Syndrome / Q000201:enzymology* / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D006419:Heme Oxygenase (Decyclizing)