BACKGROUND: Heme-oxygenase (HO)-1 acts as an inducible defense against oxidative stress and could play an important role in inflammation models, providing protection against oxidative stress and systemic inflammatory response. The objective of this study was to improve the role of HO-1 on systemic inflammatory response in an endotoxic shock model. METHODS: Five groups of animals were used: control group; lipopolysaccharide (LPS) group, animals received LPS 5 mg/kg; hemin + LPS group, animals received pretreatment with hemin, used to induce HO-1 expression; Zn-PP group, animals received Zn-PP, a specific inhibitor of HO-1 activity and hemin group. At the end of the experiment, tissue and blood samples were isolated for the measurement of HO-1 mRNA expression, biochemical measurements, and cytokine measurements. RESULTS: HO-1 messenger RNA expression and protein were induced to a larger extent in LPS group in distal organs. Hemin pretreatment induced a significant decrease oxidative stress and tumor necrosis factor-alpha plasma levels with a significant increase of interleukin-10 plasma levels. Pulmonary injury was markedly limited after hemin. Onset of lethality in LPS group occurred at H6, and was delayed until H10 with hemin. Inhibition of HO-1 activity by Zn-PP administration abolished the beneficial effect of hemin-pretreatment. CONCLUSIONS: Early HO-1 expression may modulate systemic inflammatory response and limit end-organ injury in endotoxic shock model.
BACKGROUND:Heme-oxygenase (HO)-1 acts as an inducible defense against oxidative stress and could play an important role in inflammation models, providing protection against oxidative stress and systemic inflammatory response. The objective of this study was to improve the role of HO-1 on systemic inflammatory response in an endotoxic shock model. METHODS: Five groups of animals were used: control group; lipopolysaccharide (LPS) group, animals received LPS 5 mg/kg; hemin + LPS group, animals received pretreatment with hemin, used to induce HO-1 expression; Zn-PP group, animals received Zn-PP, a specific inhibitor of HO-1 activity and hemin group. At the end of the experiment, tissue and blood samples were isolated for the measurement of HO-1 mRNA expression, biochemical measurements, and cytokine measurements. RESULTS:HO-1 messenger RNA expression and protein were induced to a larger extent in LPS group in distal organs. Hemin pretreatment induced a significant decrease oxidative stress and tumor necrosis factor-alpha plasma levels with a significant increase of interleukin-10 plasma levels. Pulmonary injury was markedly limited after hemin. Onset of lethality in LPS group occurred at H6, and was delayed until H10 with hemin. Inhibition of HO-1 activity by Zn-PP administration abolished the beneficial effect of hemin-pretreatment. CONCLUSIONS: Early HO-1 expression may modulate systemic inflammatory response and limit end-organ injury in endotoxic shock model.
Authors: Aida Habtezion; Raymond Kwan; Alice L Yang; Maureen E Morgan; Ehsaan Akhtar; Stephen P Wanaski; Stephen D Collins; Eugene C Butcher; Ahmad Kamal; M Bishr Omary Journal: Am J Physiol Gastrointest Liver Physiol Date: 2010-10-21 Impact factor: 4.052
Authors: K Shimizu; S J Bae; T Hara; Y Iwata; T Yamaoka; K Komura; E Muroi; M Takenaka; F Ogawa; S Sato Journal: Clin Exp Immunol Date: 2008-05-26 Impact factor: 4.330