Protective role of heme oxygenases against endotoxin-induced diaphragmatic dysfunction in rats
| Autor: | Michel Aubier, Sophie Lanone, Roberto Motterlini, Colin J. Green, Camille Taillé, Jorge Boczkowski, Christine Zedda, Roberta Foresti |
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| Předmět: |
Male
Pulmonary and Respiratory Medicine medicine.medical_specialty Pathology Oxygenase Lipopolysaccharide Diaphragm Protoporphyrins Diaphragmatic breathing Critical Care and Intensive Care Medicine medicine.disease_cause Rats Sprague-Dawley chemistry.chemical_compound Malondialdehyde Internal medicine medicine Animals Heme Escherichia coli Infections chemistry.chemical_classification Reactive oxygen species business.industry Endotoxemia Rats Endotoxins Heme oxygenase Endocrinology chemistry Heme Oxygenase (Decyclizing) business Oxidative stress Hemin |
| Zdroj: | ResearcherID |
| Popis: | Reactive oxygen species are strongly implicated in diaphragmatic dysfunction during sepsis. We investigated whether the heme oxygenase (HO) pathway, which is a powerful protective cellular system, protects the diaphragm against oxidative stress and contractile failure during sepsis. A basal expression of both the inducible and constitutive HO protein isoforms (HO-1 and HO-2, respectively) was found in the diaphragm. Enhanced HO-1 expression in diaphragmatic myocytes was observed 24 h after Escherichia coli endotoxin (lipopolysaccharide, LPS) inoculation and remained elevated for at least 96 h. Enhanced HO-1 expression was also observed in the rectus abdominis and soleus muscles and in the left ventricular myocardium of endotoxemic animals. Diaphragmatic HO-2 expression was not modified by endotoxin. Diaphragmatic HO activity exhibited a biphasic time course characterized by a transient decrease during the first 12 h followed by a significant increase at 24 h, corresponding to HO-1 induction. Diaphragmatic force was significantly reduced 24 h after LPS, concomitantly with muscular oxidative stress. Administation of an inhibitor of heme oxygenase activity, zinc protoporphyrin IX (ZnPP-IX), further impaired muscular oxidative stress and contractile failure. By contrast, increased levels of HO-1 expression obtained by pretreatment of rats with hemin, a powerful inducer of HO-1, completely prevented LPS-mediated diaphragmatic oxidative stress and contractile failure. This protective effect was reversed by ZnPP-IX. These results show an important protective role for the HO pathway against sepsis-induced diaphragmatic dysfunction, which could be related to its antioxidant properties. |
| Databáze: | OpenAIRE |
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