Cargando…

Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment

OBJECTIVES: Experimental studies on sepsis have demonstrated that ethyl pyruvate is endowed with antioxidant and anti-inflammatory properties. This study aimed to investigate the effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation in a live Escherichia...

Descripción completa

Detalles Bibliográficos
Autores principales: Guarda, Ismael Francisco Mota Siqueira, Correia, Cristiano Jesus, Breithaupt-Faloppa, Ana Cristina, Ferreira, Sueli Gomes, Moreno, Ana Carolina Ramos, Martinez, Marina Baquerizo, Rocha-e-Silva, Mauricio, Sannomiya, Paulina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496755/
https://www.ncbi.nlm.nih.gov/pubmed/26222821
http://dx.doi.org/10.6061/clinics/2015(07)08
_version_ 1782380455043006464
author Guarda, Ismael Francisco Mota Siqueira
Correia, Cristiano Jesus
Breithaupt-Faloppa, Ana Cristina
Ferreira, Sueli Gomes
Moreno, Ana Carolina Ramos
Martinez, Marina Baquerizo
Rocha-e-Silva, Mauricio
Sannomiya, Paulina
author_facet Guarda, Ismael Francisco Mota Siqueira
Correia, Cristiano Jesus
Breithaupt-Faloppa, Ana Cristina
Ferreira, Sueli Gomes
Moreno, Ana Carolina Ramos
Martinez, Marina Baquerizo
Rocha-e-Silva, Mauricio
Sannomiya, Paulina
author_sort Guarda, Ismael Francisco Mota Siqueira
collection PubMed
description OBJECTIVES: Experimental studies on sepsis have demonstrated that ethyl pyruvate is endowed with antioxidant and anti-inflammatory properties. This study aimed to investigate the effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation in a live Escherichia coli-induced sepsis model in rats. METHODS: Male Wistar rats were administered an intravenous suspension of E. coli bacteria or were subjected to a sham procedure. Three hours after bacterial infusion, the rats were randomized into the following groups: a control group without treatment, a group treated with lactated Ringer's solution (4 mL/kg, i.v.), and a group treated with lactated Ringer's solution (4 mL/kg, i.v.) plus ethyl pyruvate (50 mg/kg). At 24 h after bacterial infusion, leukocyte-endothelial interactions were investigated using intravital microscopy, and the expression of P-selectin and intercellular adhesion molecule-1 was evaluated via immunohistochemistry. White blood cell and platelet counts were also determined at baseline and 3 h and 24 h after E. coli inoculation. RESULTS: The non-treated and lactated Ringer's solution-treated groups exhibited increases in the numbers of rolling leukocytes (∼2.5-fold increase), adherent cells (∼3.0-fold), and migrated cells (∼3.5-fold) compared with the sham group. In contrast, treatment with Ringer's ethyl pyruvate solution reduced the numbers of rolling, adherent and migrated leukocytes to the levels observed in the sham group. Additionally, the expression of P-selectin and intercellular adhesion molecule-1 was significantly increased on mesenteric microvessels in the non-treated group compared with the sham group (p<0.001). The expression of both adhesion molecules was reduced in the other groups, with ethyl pyruvate being more effective than lactated Ringer's solution. Infusion of bacteria caused significant leukopenia (3 h), followed by leukocytosis with granulocytosis (24 h). There was also an intense and progressive reduction in the number of platelets. However, no differences were observed after treatment with the different solutions. CONCLUSIONS: The presented data suggest that ethyl pyruvate efficiently reduces the inflammatory response in the mesenteric microcirculation in an experimental model of sepsis induced by live E. coli and is associated, at least in part, with down-regulation of P-selectin and intercellular adhesion molecule-1.
format Online
Article
Text
id pubmed-4496755
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
record_format MEDLINE/PubMed
spelling pubmed-44967552015-07-13 Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment Guarda, Ismael Francisco Mota Siqueira Correia, Cristiano Jesus Breithaupt-Faloppa, Ana Cristina Ferreira, Sueli Gomes Moreno, Ana Carolina Ramos Martinez, Marina Baquerizo Rocha-e-Silva, Mauricio Sannomiya, Paulina Clinics (Sao Paulo) Basic Research OBJECTIVES: Experimental studies on sepsis have demonstrated that ethyl pyruvate is endowed with antioxidant and anti-inflammatory properties. This study aimed to investigate the effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation in a live Escherichia coli-induced sepsis model in rats. METHODS: Male Wistar rats were administered an intravenous suspension of E. coli bacteria or were subjected to a sham procedure. Three hours after bacterial infusion, the rats were randomized into the following groups: a control group without treatment, a group treated with lactated Ringer's solution (4 mL/kg, i.v.), and a group treated with lactated Ringer's solution (4 mL/kg, i.v.) plus ethyl pyruvate (50 mg/kg). At 24 h after bacterial infusion, leukocyte-endothelial interactions were investigated using intravital microscopy, and the expression of P-selectin and intercellular adhesion molecule-1 was evaluated via immunohistochemistry. White blood cell and platelet counts were also determined at baseline and 3 h and 24 h after E. coli inoculation. RESULTS: The non-treated and lactated Ringer's solution-treated groups exhibited increases in the numbers of rolling leukocytes (∼2.5-fold increase), adherent cells (∼3.0-fold), and migrated cells (∼3.5-fold) compared with the sham group. In contrast, treatment with Ringer's ethyl pyruvate solution reduced the numbers of rolling, adherent and migrated leukocytes to the levels observed in the sham group. Additionally, the expression of P-selectin and intercellular adhesion molecule-1 was significantly increased on mesenteric microvessels in the non-treated group compared with the sham group (p<0.001). The expression of both adhesion molecules was reduced in the other groups, with ethyl pyruvate being more effective than lactated Ringer's solution. Infusion of bacteria caused significant leukopenia (3 h), followed by leukocytosis with granulocytosis (24 h). There was also an intense and progressive reduction in the number of platelets. However, no differences were observed after treatment with the different solutions. CONCLUSIONS: The presented data suggest that ethyl pyruvate efficiently reduces the inflammatory response in the mesenteric microcirculation in an experimental model of sepsis induced by live E. coli and is associated, at least in part, with down-regulation of P-selectin and intercellular adhesion molecule-1. Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo 2015-07 2015-07 /pmc/articles/PMC4496755/ /pubmed/26222821 http://dx.doi.org/10.6061/clinics/2015(07)08 Text en Copyright © 2015 Clinics http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Basic Research
Guarda, Ismael Francisco Mota Siqueira
Correia, Cristiano Jesus
Breithaupt-Faloppa, Ana Cristina
Ferreira, Sueli Gomes
Moreno, Ana Carolina Ramos
Martinez, Marina Baquerizo
Rocha-e-Silva, Mauricio
Sannomiya, Paulina
Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment
title Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment
title_full Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment
title_fullStr Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment
title_full_unstemmed Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment
title_short Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment
title_sort effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment
topic Basic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496755/
https://www.ncbi.nlm.nih.gov/pubmed/26222821
http://dx.doi.org/10.6061/clinics/2015(07)08
work_keys_str_mv AT guardaismaelfranciscomotasiqueira effectsofethylpyruvateonleukocyteendothelialinteractionsinthemesentericmicrocirculationduringearlysepsistreatment
AT correiacristianojesus effectsofethylpyruvateonleukocyteendothelialinteractionsinthemesentericmicrocirculationduringearlysepsistreatment
AT breithauptfaloppaanacristina effectsofethylpyruvateonleukocyteendothelialinteractionsinthemesentericmicrocirculationduringearlysepsistreatment
AT ferreirasueligomes effectsofethylpyruvateonleukocyteendothelialinteractionsinthemesentericmicrocirculationduringearlysepsistreatment
AT morenoanacarolinaramos effectsofethylpyruvateonleukocyteendothelialinteractionsinthemesentericmicrocirculationduringearlysepsistreatment
AT martinezmarinabaquerizo effectsofethylpyruvateonleukocyteendothelialinteractionsinthemesentericmicrocirculationduringearlysepsistreatment
AT rochaesilvamauricio effectsofethylpyruvateonleukocyteendothelialinteractionsinthemesentericmicrocirculationduringearlysepsistreatment
AT sannomiyapaulina effectsofethylpyruvateonleukocyteendothelialinteractionsinthemesentericmicrocirculationduringearlysepsistreatment