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  1. Article ; Online: Inhibition of endogenous glucocorticoid synthesis aggravates lung injury triggered by septic shock in rats.

    Incerpi, Erika K / Oliveira, Luiz M / Pereira, Elisângela M / Soncini, Roseli

    International journal of experimental pathology

    2015  Volume 96, Issue 3, Page(s) 133–139

    Abstract: 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 ... ...

    Abstract 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 (H2 O2 ) 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.
    MeSH term(s) Acute Lung Injury/blood ; Acute Lung Injury/chemically induced ; Acute Lung Injury/pathology ; Acute Lung Injury/physiopathology ; Animals ; Corticosterone/biosynthesis ; Corticosterone/blood ; Disease Models, Animal ; Down-Regulation ; Enzyme Inhibitors/toxicity ; Hydrogen Peroxide/metabolism ; Inflammation Mediators/metabolism ; Lung/drug effects ; Lung/metabolism ; Lung/pathology ; Lung/physiopathology ; Male ; Metyrapone/toxicity ; Oxidative Stress/drug effects ; Rats, Wistar ; Respiratory Mechanics/drug effects ; Shock, Septic/complications ; Steroid 11-beta-Hydroxylase/antagonists & inhibitors ; Steroid 11-beta-Hydroxylase/metabolism ; Time Factors
    Chemical Substances Enzyme Inhibitors ; Inflammation Mediators ; Hydrogen Peroxide (BBX060AN9V) ; Steroid 11-beta-Hydroxylase (EC 1.14.15.4) ; Corticosterone (W980KJ009P) ; Metyrapone (ZS9KD92H6V)
    Language English
    Publishing date 2015-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1016006-1
    ISSN 1365-2613 ; 0958-4625 ; 0007-1021 ; 0959-9673
    ISSN (online) 1365-2613
    ISSN 0958-4625 ; 0007-1021 ; 0959-9673
    DOI 10.1111/iep.12113
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Glucocorticoid receptor gene expression in a CLP-induced ARDS-like rat model treated with dexamethasone and metyrapone.

    Soncini, Roseli / Vieira, Joseana / Ramos Lopes, Ana Carolina / Ruginsk, Silvia Graciela / Incerpi, Erika K / Barchuk, Angel Roberto

    Molecular and cellular endocrinology

    2018  Volume 474, Page(s) 151–157

    Abstract: Glucocorticoids (GCs) are used for acute respiratory distress syndrome (ARDS) to improve or prevent lung injury. The mechanisms underlying the effects of GCs involve inadequate GC-receptor (GR)-mediated downregulation of pro-inflammatory factors despite ... ...

    Abstract Glucocorticoids (GCs) are used for acute respiratory distress syndrome (ARDS) to improve or prevent lung injury. The mechanisms underlying the effects of GCs involve inadequate GC-receptor (GR)-mediated downregulation of pro-inflammatory factors despite elevated levels of cortisol. Within this context, knowledge of the transcriptional pattern of the GR gene in response to variations in physiological parameters may shed light on this issue. We addressed this problem by measuring plasmatic corticosterone (CCT) levels and assessing GR expression at transcript and protein levels in rats with caecal ligation and puncture (CLP)-induced ARDS-like syndrome treated with dexamethasone and metyrapone. Seventy male rats were randomized into three main groups: Naïve (any treatment), Sham (caecum-exposed) and CLP. CLP animals were divided into three groups according to pretreatments performed before surgery: CLP sal (0.9% NaCl ip), CLP metyrapone (50 mg.kg-1 ip) and CLP dexamethasone (0.5 mg.kg-1 ip). Our results showed that CLP sal promotes elevation in CCT levels, which are significantly reduced with metyrapone to levels comparable to untreated animals when dexamethasone is used. In this hormonal milieu, the GR gene transcript levels of both variants, GRα and GRβ, are produced in comparable levels and in response to caecum-exposing surgery. Nonetheless, the expression of the GRα variant demonstrated positive sensitivity to variations in CCT levels and was downregulated in animals treated with dexamethasone. Moreover, nuclear translocation of GR protein decreased with high levels of plasma CCT and higher GR translocation was found in animals with moderate CCT levels; in either case, the process seemed to be positively associated with the CLP procedure.
    MeSH term(s) Animals ; Cecum/pathology ; Corticosterone/blood ; Dexamethasone/pharmacology ; Dexamethasone/therapeutic use ; Disease Models, Animal ; Gene Expression Regulation/drug effects ; Ligation ; Male ; Metyrapone/pharmacology ; Metyrapone/therapeutic use ; Punctures ; Rats, Wistar ; Receptors, Glucocorticoid/genetics ; Receptors, Glucocorticoid/metabolism ; Respiratory Distress Syndrome, Adult/drug therapy ; Respiratory Distress Syndrome, Adult/genetics ; Respiratory Distress Syndrome, Adult/pathology ; Transcription, Genetic
    Chemical Substances Receptors, Glucocorticoid ; Dexamethasone (7S5I7G3JQL) ; Corticosterone (W980KJ009P) ; Metyrapone (ZS9KD92H6V)
    Language English
    Publishing date 2018-03-06
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2018.03.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Glucocorticoid receptor gene expression in a CLP-induced ARDS-like rat model treated with dexamethasone and metyrapone

    Soncini, Roseli / Ana Carolina Ramos Lopes / Angel Roberto Barchuk / Erika K. Incerpi / Joseana Vieira / Silvia Graciela Ruginsk

    Molecular and cellular endocrinology. 2018 Oct. 15, v. 474

    2018  

    Abstract: Glucocorticoids (GCs) are used for acute respiratory distress syndrome (ARDS) to improve or prevent lung injury. The mechanisms underlying the effects of GCs involve inadequate GC-receptor (GR)-mediated downregulation of pro-inflammatory factors despite ... ...

    Abstract Glucocorticoids (GCs) are used for acute respiratory distress syndrome (ARDS) to improve or prevent lung injury. The mechanisms underlying the effects of GCs involve inadequate GC-receptor (GR)-mediated downregulation of pro-inflammatory factors despite elevated levels of cortisol. Within this context, knowledge of the transcriptional pattern of the GR gene in response to variations in physiological parameters may shed light on this issue. We addressed this problem by measuring plasmatic corticosterone (CCT) levels and assessing GR expression at transcript and protein levels in rats with caecal ligation and puncture (CLP)-induced ARDS-like syndrome treated with dexamethasone and metyrapone. Seventy male rats were randomized into three main groups: Naïve (any treatment), Sham (caecum-exposed) and CLP. CLP animals were divided into three groups according to pretreatments performed before surgery: CLP sal (0.9% NaCl ip), CLP metyrapone (50 mg.kg-1 ip) and CLP dexamethasone (0.5 mg.kg-1 ip). Our results showed that CLP sal promotes elevation in CCT levels, which are significantly reduced with metyrapone to levels comparable to untreated animals when dexamethasone is used. In this hormonal milieu, the GR gene transcript levels of both variants, GRα and GRβ, are produced in comparable levels and in response to caecum-exposing surgery. Nonetheless, the expression of the GRα variant demonstrated positive sensitivity to variations in CCT levels and was downregulated in animals treated with dexamethasone. Moreover, nuclear translocation of GR protein decreased with high levels of plasma CCT and higher GR translocation was found in animals with moderate CCT levels; in either case, the process seemed to be positively associated with the CLP procedure.
    Keywords acute respiratory distress syndrome ; animal models ; cecum ; corticosterone ; cortisol ; dexamethasone ; gene expression ; genes ; glucocorticoid receptors ; lungs ; males ; messenger RNA ; metyrapone ; protein content ; rats ; sodium chloride ; surgery ; transcription (genetics)
    Language English
    Dates of publication 2018-1015
    Size p. 151-157.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2018.03.001
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Postnatal overnutrition in mice leads to impaired pulmonary mechanics in response to salbutamol.

    Teixeira, Vanessa P / Cervilha, Daniela A B / Cabral, Layla D M / Oliveira, Luiz M / Incerpi, Erika K / Novaes, Rômulo D / Ionta, Marisa / Soncini, Roseli

    The journal of physiological sciences : JPS

    2015  Volume 66, Issue 3, Page(s) 221–228

    Abstract: Obesity increases the risk of respiratory disease, which is associated with airway hyperresponsiveness. Although the molecular underpinnings of this phenomenon are not well established, lung remodeling is known as an important factor in this process and ... ...

    Abstract Obesity increases the risk of respiratory disease, which is associated with airway hyperresponsiveness. Although the molecular underpinnings of this phenomenon are not well established, lung remodeling is known as an important factor in this process and could potentially explain compromised lung functions. In the present study, the obesity was induced by postnatal overnutrition in Swiss mice and we investigated the pulmonary mechanics after aerosolization of saline, methacholine, and salbutamol. The lungs were prepared for morphometric analysis. Obese animals showed bronchoconstriction in response to methacholine, as evidenced by airway and tissue resistance, tissue elastance, and hysteresivity. Salbutamol was effective at recovering the response only for airway resistance but not for tissue mechanics. We suggest that this impaired response in obese mice is related to collapsed alveolar, to inflammatory cells, and to elevated deposition collagen fibers in parenchymal tissue.
    MeSH term(s) Albuterol/pharmacology ; Animals ; Animals, Newborn ; Bronchodilator Agents/pharmacology ; Female ; Lung/drug effects ; Lung/physiology ; Male ; Mice ; Obesity/complications ; Overnutrition/physiopathology ; Respiratory Physiological Phenomena/drug effects
    Chemical Substances Bronchodilator Agents ; Albuterol (QF8SVZ843E)
    Language English
    Publishing date 2015-10-23
    Publishing country Japan
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2234472-X
    ISSN 1880-6562 ; 1880-6546
    ISSN (online) 1880-6562
    ISSN 1880-6546
    DOI 10.1007/s12576-015-0417-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Efeito anti-inflamatório da lipoproteína de alta densidade no sistema cardiovascular de camundongos hiperlipidêmicos.

    Garcia, José Antonio D / de Lima, Ciderléia Castro / Messora, Luiza B / Cruz, Aline F / Marques, Ana P S / Simão, Talita P / Soares, Evelise Aline / Cristina Costa Resck, M / Incerpi, Erika K / de Mello Oliveira, Nelma / dos Santos, Leandro

    Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology

    2011  Volume 30, Issue 10, Page(s) 763–769

    Abstract: Introduction: LDLr-/- mice are spontaneously hyperlipidemic and resistant to the development of neointimal lesions.: Objectives: This study aimed to determine the factor that prevents the inflammatory process and neointimal lesions and insulin ... ...

    Title translation Anti-inflammatory effect of high-density lipoprotein on the cardiovascular system of hyperlipidemic mice.
    Abstract Introduction: LDLr-/- mice are spontaneously hyperlipidemic and resistant to the development of neointimal lesions.
    Objectives: This study aimed to determine the factor that prevents the inflammatory process and neointimal lesions and insulin resistance in LDLr-/- mice.
    Methods: Three groups of 3-month-old male mice were used: wild-type mice (WT group); LDLr-/- mice fed a standard diet (S group); and LDLr-/- mice fed a high-fat diet (HF group). After 15 days, blood was collected for analysis of plasma lipids, glucose and insulin. The HOMA index was calculated to determine insulin resistance. The heart and aorta were removed for histological study. Histological sections of the heart were processed immunohistochemically with anti-CD40L antibodies to evaluate the inflammatory process. Histological sections of the aorta were stained with hematoxylin/eosin and picrosirius red to assess morphological and morphometric alterations.
    Results: The S mice were resistant to the inflammatory process, as shown by low immunoreactivity to CD40L, with high plasma HDL levels, and did not develop insulin resistance, even with moderate hyperlipidemia compared to WT. The HF mice showed severe hyperlipidemia, increased cardiac immunoreactivity to CD40L, pronounced morphological changes in the aortic wall and insulin resistance, associated with a decrease in plasma HDL levels, compared to S. This severe hyperlipidemia in the HF mice can be considered the major metabolic factor inducing oxidative stress in the cardiovascular system, increasing the lipid peroxidation of HDL and hence its removal by the liver, with consequent lowering of plasma HDL levels.
    Conclusion: High HDL plasma levels are a protective factor against the development of cardiovascular inflammation and insulin resistance in LDLr-/- mice, preventing the development of neointimal lesions.
    MeSH term(s) Animals ; Cardiovascular System/pathology ; Humans ; Hyperlipidemias/blood ; Hyperlipidemias/complications ; Inflammation/blood ; Inflammation/etiology ; Inflammation/prevention & control ; Lipoproteins, HDL/blood ; Lipoproteins, HDL/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Neointima/pathology
    Chemical Substances Lipoproteins, HDL
    Language Portuguese
    Publishing date 2011-10
    Publishing country Portugal
    Document type English Abstract ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 632718-7
    ISSN 0870-2551 ; 0304-4750
    ISSN 0870-2551 ; 0304-4750
    DOI 10.1016/S0870-2551(11)70024-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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