Inhibition of endogenous glucocorticoid synthesis aggravates lung injury triggered by septic shock in rats

Summary The aim of this study was to determine the effects of previous administration of metyrapone (met) on the acute lung injury (ALI) induced by caecal ligation and puncture (CLP) and to explore met's relationship with endogenous glucocorticoids (GCs) as measured by inflammatory, oxidative a...

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Published in:	International journal of experimental pathology Vol. 96; no. 3; pp. 133 - 139
Main Authors:	Incerpi, Erika K., Oliveira, Luiz M., Pereira, Elisângela M., Soncini, Roseli
Format:	Journal Article
Language:	English
Published:	England Blackwell Publishing Ltd 01-06-2015 John Wiley & Sons, Ltd
Subjects:	Acute Lung Injury - blood Acute Lung Injury - chemically induced Acute Lung Injury - pathology Acute Lung Injury - physiopathology acute lung injury/acute respiratory distress syndrome Animals Corticosterone - biosynthesis Corticosterone - blood Disease Models, Animal Down-Regulation Enzyme Inhibitors - toxicity glucocorticoids Hydrogen Peroxide - metabolism Inflammation Mediators - metabolism Lung - drug effects Lung - metabolism Lung - pathology Lung - physiopathology Male metyrapone Metyrapone - toxicity Original Oxidative Stress - drug effects Rats, Wistar Respiratory Mechanics - drug effects sepsis Shock, Septic - complications Steroid 11-beta-Hydroxylase - antagonists & inhibitors Steroid 11-beta-Hydroxylase - metabolism Time Factors acute lung injury/acute respiratory distress syndrome metyrapone glucocorticoids sepsis
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Summary:	Summary The aim of this study was to determine the effects of previous administration of metyrapone (met) on the acute lung injury (ALI) induced by caecal ligation and puncture (CLP) and to explore met's relationship with endogenous glucocorticoids (GCs) as measured by inflammatory, oxidative and functional parameters. One hundred and thirty‐five Wistar rats were divided into three main groups: Control (Naïve), Sham and CLP. The animals received pretreatment one hour before surgery. The Naïve group did not undergo any procedure or pretreatment. The Sham group only had the caecum exposed and was pretreated with saline. The CLP group was divided into three pretreatments: metyrapone (CLP met 50 mg/kg i.p.), dexamethasone (CLP dex 0.5 mg/kg i.p.) or saline (CLP sal equivalent volume of 0.9% NaCl). Analyses were performed after 6 and 24 h of sepsis. Previous administration of met significantly increased inflammatory cells, as well as myeloperoxidase (MPO) activity in the lung tissue and alveolar collapsed area, with consequent impairment of respiratory mechanics being observed compared to Sham and Naïve; CLP sal exhibited similar results to those of met. The met reduced corticosterone (CCT) levels and dramatically increased hydrogen peroxide (H2O2) levels in the lung tissue compared to CLP sal. Our results suggest that previous administration of met may have contributed to increased pulmonary oxidative stress and increased mortality by mechanisms dependent of endogenous GC.
Bibliography:	ark:/67375/WNG-C71ZRX2C-1 FAPEMIG - No. APQ-02534/10; No. APQ-01887/13 ArticleID:IEP12113 istex:4DBF2E20D876D1F80E94230EF76FAC45CC512A53 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0959-9673 1365-2613
DOI:	10.1111/iep.12113