Abstract | BACKGROUND: 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.
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Authors | Cherif N Boutros, Rachid Zegdi, Nermine Lila, Michele Combillau, Paul Fornes, Alain Carpentier, Jean Noel Fabiani |
Journal | The Journal of surgical research
(J Surg Res)
Vol. 129
Issue 2
Pg. 306-12
(Dec 2005)
ISSN: 0022-4804 [Print] United States |
PMID | 16140332
(Publication Type: Journal Article)
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Chemical References |
- Coloring Agents
- Enzyme Inhibitors
- Protoporphyrins
- zinc protoporphyrin
- Evans Blue
- Heme Oxygenase-1
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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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