Cargando…

Atorvastatin and diacerein reduce insulin resistance and increase disease tolerance in rats with sepsis

BACKGROUND: Sepsis is one of the leading causes of death among hospitalized patients. At the onset of this condition, there is an over-production of pro-inflammatory mediators that contribute to organ failure and death. The excess production of pro-inflammatory mediators also impairs insulin signali...

Descripción completa

Detalles Bibliográficos
Autores principales: da Silva, K. L. C., Camacho, A. P., Mittestainer, F. C., Carvalho, B. M., Santos, A., Guadagnini, D., Oliveira, A. G., Saad, M. J. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944072/
https://www.ncbi.nlm.nih.gov/pubmed/29760586
http://dx.doi.org/10.1186/s12950-018-0184-9
_version_ 1783321754440040448
author da Silva, K. L. C.
Camacho, A. P.
Mittestainer, F. C.
Carvalho, B. M.
Santos, A.
Guadagnini, D.
Oliveira, A. G.
Saad, M. J. A.
author_facet da Silva, K. L. C.
Camacho, A. P.
Mittestainer, F. C.
Carvalho, B. M.
Santos, A.
Guadagnini, D.
Oliveira, A. G.
Saad, M. J. A.
author_sort da Silva, K. L. C.
collection PubMed
description BACKGROUND: Sepsis is one of the leading causes of death among hospitalized patients. At the onset of this condition, there is an over-production of pro-inflammatory mediators that contribute to organ failure and death. The excess production of pro-inflammatory mediators also impairs insulin signaling, which may be a pathophysiological tissue marker of proinflammatory cytokine action before organ failure. Statins and diacerein have pleiotropic effects, such as the blockage of inflammatory signaling pathways, suggesting that these drugs may be an attractive therapeutic or prophylactic strategy against sepsis. The aim of the present study was to investigate whether a statin or diacerein can improve insulin signaling, disease tolerance and survival in sepsis by inhibiting inflammatory pathways. METHODS: We investigated the effect of these drugs on survival, tissue insulin signaling and inflammatory pathways in the liver and muscle of rats with sepsis induced by cecal ligation and puncture (CLP). RESULTS: The results showed that administration of medications, with anti-inflammatory ability, to septic animals increased survival and improved disease tolerance and insulin resistance in the liver and muscle. The treatment also attenuated ER stress, NF-κB, JNK activation and restored glucose-6-phosphatase (G6Pase) levels in the liver. CONCLUSIONS: Our results indicate that atorvastatin and diacerein treatment can modulate inflammatory pathways and, in parallel, attenuate insulin resistance in sepsis. Since these two drugs have safety profiles and minimal side effects, we suggest that these drugs may be alternative therapies for the prevention or therapies for the treatment of insulin resistance in sepsis, which could potentially reduce mortality in patients with sepsis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12950-018-0184-9) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-5944072
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-59440722018-05-14 Atorvastatin and diacerein reduce insulin resistance and increase disease tolerance in rats with sepsis da Silva, K. L. C. Camacho, A. P. Mittestainer, F. C. Carvalho, B. M. Santos, A. Guadagnini, D. Oliveira, A. G. Saad, M. J. A. J Inflamm (Lond) Research BACKGROUND: Sepsis is one of the leading causes of death among hospitalized patients. At the onset of this condition, there is an over-production of pro-inflammatory mediators that contribute to organ failure and death. The excess production of pro-inflammatory mediators also impairs insulin signaling, which may be a pathophysiological tissue marker of proinflammatory cytokine action before organ failure. Statins and diacerein have pleiotropic effects, such as the blockage of inflammatory signaling pathways, suggesting that these drugs may be an attractive therapeutic or prophylactic strategy against sepsis. The aim of the present study was to investigate whether a statin or diacerein can improve insulin signaling, disease tolerance and survival in sepsis by inhibiting inflammatory pathways. METHODS: We investigated the effect of these drugs on survival, tissue insulin signaling and inflammatory pathways in the liver and muscle of rats with sepsis induced by cecal ligation and puncture (CLP). RESULTS: The results showed that administration of medications, with anti-inflammatory ability, to septic animals increased survival and improved disease tolerance and insulin resistance in the liver and muscle. The treatment also attenuated ER stress, NF-κB, JNK activation and restored glucose-6-phosphatase (G6Pase) levels in the liver. CONCLUSIONS: Our results indicate that atorvastatin and diacerein treatment can modulate inflammatory pathways and, in parallel, attenuate insulin resistance in sepsis. Since these two drugs have safety profiles and minimal side effects, we suggest that these drugs may be alternative therapies for the prevention or therapies for the treatment of insulin resistance in sepsis, which could potentially reduce mortality in patients with sepsis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12950-018-0184-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-05-09 /pmc/articles/PMC5944072/ /pubmed/29760586 http://dx.doi.org/10.1186/s12950-018-0184-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
da Silva, K. L. C.
Camacho, A. P.
Mittestainer, F. C.
Carvalho, B. M.
Santos, A.
Guadagnini, D.
Oliveira, A. G.
Saad, M. J. A.
Atorvastatin and diacerein reduce insulin resistance and increase disease tolerance in rats with sepsis
title Atorvastatin and diacerein reduce insulin resistance and increase disease tolerance in rats with sepsis
title_full Atorvastatin and diacerein reduce insulin resistance and increase disease tolerance in rats with sepsis
title_fullStr Atorvastatin and diacerein reduce insulin resistance and increase disease tolerance in rats with sepsis
title_full_unstemmed Atorvastatin and diacerein reduce insulin resistance and increase disease tolerance in rats with sepsis
title_short Atorvastatin and diacerein reduce insulin resistance and increase disease tolerance in rats with sepsis
title_sort atorvastatin and diacerein reduce insulin resistance and increase disease tolerance in rats with sepsis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944072/
https://www.ncbi.nlm.nih.gov/pubmed/29760586
http://dx.doi.org/10.1186/s12950-018-0184-9
work_keys_str_mv AT dasilvaklc atorvastatinanddiacereinreduceinsulinresistanceandincreasediseasetoleranceinratswithsepsis
AT camachoap atorvastatinanddiacereinreduceinsulinresistanceandincreasediseasetoleranceinratswithsepsis
AT mittestainerfc atorvastatinanddiacereinreduceinsulinresistanceandincreasediseasetoleranceinratswithsepsis
AT carvalhobm atorvastatinanddiacereinreduceinsulinresistanceandincreasediseasetoleranceinratswithsepsis
AT santosa atorvastatinanddiacereinreduceinsulinresistanceandincreasediseasetoleranceinratswithsepsis
AT guadagninid atorvastatinanddiacereinreduceinsulinresistanceandincreasediseasetoleranceinratswithsepsis
AT oliveiraag atorvastatinanddiacereinreduceinsulinresistanceandincreasediseasetoleranceinratswithsepsis
AT saadmja atorvastatinanddiacereinreduceinsulinresistanceandincreasediseasetoleranceinratswithsepsis