Protective effects of heme-oxygenase expression against endotoxic shock: inhibition of tumor necrosis factor-alpha and augmentation of interleukin-10.

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.
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.
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.
Early HO-1 expression may modulate systemic inflammatory response and limit end-organ injury in endotoxic shock model.
AuthorsFabienne Tamion, Vincent Richard, Sylvanie Renet, Christian Thuillez
JournalThe Journal of trauma (J Trauma) Vol. 61 Issue 5 Pg. 1078-84 (Nov 2006) ISSN: 0022-5282 [Print] United States
PMID17099512 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Protoporphyrins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • zinc protoporphyrin
  • Hemin
  • Heme Oxygenase-1
  • Animals
  • Disease Models, Animal
  • Enzyme Inhibitors (pharmacology, therapeutic use)
  • Heme Oxygenase-1 (metabolism)
  • Hemin (pharmacology, therapeutic use)
  • Interleukin-10 (blood)
  • Intestines (metabolism)
  • Lipopolysaccharides
  • Lung (metabolism)
  • Lung Injury
  • Male
  • Myocardium (metabolism)
  • Oxidative Stress (drug effects, physiology)
  • Protoporphyrins (pharmacology, therapeutic use)
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Shock, Septic (drug therapy, metabolism, mortality)
  • Tumor Necrosis Factor-alpha (drug effects, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: