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Pulmonary expression of inducible heme-oxygenase after ischemia/reperfusion of the lower extremities in rats.

AbstractBACKGROUND:
Expression of inducible heme-oxygenase (HO-1) has been shown to be increased in various inflammatory disorders, which may confer a protective role. The aim of our study was to assess pulmonary expression of HO-1 after ischemia/reperfusion (I/R) of the lower limbs in rats.
MATERIALS AND METHODS:
We compared three groups of rats (n = 5/group): one Sham group, and two I/R groups (aorta cross-clamped for 2 h followed by 2 h of reperfusion), one of which pre-treated with Zn-protoporphyrin (Zn-PP), a competitive inhibitor of HO (50 micromol/kg, i.p.). At the end of experiment, lungs were harvested for determination of HO activity and HO-1 expression by Western blot and immunohistochemistry. Lung injury was assessed by bronchoalveolar lavage, histological study, and determination of the lung Evans Blue dye content, an index of microvascular permeability.
RESULTS:
I/R of the lower limbs was responsible for acute lung injury (ALI), characterized by neutrophilic infiltration (87 +/- 20 x 10(3) neutrophils/mm(3), Sham group versus 191 +/- 38 x 10(3) neutrophils/mm(3), I/R group; P < 0.002) and an increase in lung Evans blue dye content: (74 +/- 6 microg/g, Sham group versus 122 +/- 48 microg/g, I/R group; P < 0.05). Pre-treatment with Zn-PP further increases the Evans Blue content (122 +/- 48 microg/g, I/R group versus 179 +/- 23 microg/g Zn-PP group P < 0.05) and the neutrophilic infiltration. Pulmonary heme-oxygenase activity, and HO-1 content were increased after I/R. (10.5 +/- 12 pmol bilirubin/mg protein/h, Sham group versus 101.2 +/- 66 pmol bilirubin/mg protein/h, I/R group; P < 0.02). Immunohistochemistry revealed that the expression of HO-1 was mainly localized to inflammatory cells.
CONCLUSIONS:
ALI following I/R of the lower limbs in rats is associated with an increase of pulmonary expression of HO-1, inhibition of this expression increase the severity of ALI.
AuthorsCherif N Boutros, Rachid Zegdi, Nermine Lila, Michele Combillau, Paul Fornes, Alain Carpentier, Jean Noel Fabiani
JournalThe Journal of surgical research (J Surg Res) Vol. 129 Issue 2 Pg. 306-12 (Dec 2005) ISSN: 0022-4804 [Print] United States
PMID16140332 (Publication Type: Journal Article)
Chemical References
  • Coloring Agents
  • Enzyme Inhibitors
  • Protoporphyrins
  • zinc protoporphyrin
  • Evans Blue
  • Heme Oxygenase-1
Topics
  • Animals
  • Aorta, Abdominal
  • Coloring Agents (pharmacokinetics)
  • Disease Models, Animal
  • Enzyme Inhibitors (pharmacology)
  • Evans Blue (pharmacokinetics)
  • Heme Oxygenase-1 (antagonists & inhibitors, metabolism)
  • Hindlimb (blood supply)
  • Lung (enzymology, pathology)
  • Male
  • Protoporphyrins (pharmacology)
  • Rats
  • Rats, Wistar
  • Reperfusion Injury (complications, metabolism)
  • Respiratory Distress Syndrome (etiology, metabolism, pathology)
  • Severity of Illness Index

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