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

Guarda IF, Correia CJ, Breithaupt-Faloppa AC, Ferreira SG, Moreno AC, Martinez MB, Rocha-e-Silva M, Sannomiya P - Clinics (Sao Paulo) (2015)

Bottom Line: 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.There was also an intense and progressive reduction in the number of platelets.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração do Hospital das Clínicas da Faculdade de Medicinada Universidade de São Paulo (InCor), São Paulo, SP, Brazil.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

The number of rolling (3 min), adherent (100 μm venule length) and migrated (5,000 μm2) leukocytes in the rat mesenteric microcirculation 24 h after intravenous injection of E. coli. SHAM, sham-operated rats (n=5); NT, non-treated rats (n=7); LR, lactated Ringer's solution (4 mL/kg)-treated rats (n=7); REP (4 mL/kg LR + 50 mg/kg ethyl pyruvate)-treated rats (n=6). The data are presented as the mean ± SEM. *p<0.001 versus SHAM, †p<0.001 and ?p<0.01 versus NT and LR.
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f2-clin_70p508: The number of rolling (3 min), adherent (100 μm venule length) and migrated (5,000 μm2) leukocytes in the rat mesenteric microcirculation 24 h after intravenous injection of E. coli. SHAM, sham-operated rats (n=5); NT, non-treated rats (n=7); LR, lactated Ringer's solution (4 mL/kg)-treated rats (n=7); REP (4 mL/kg LR + 50 mg/kg ethyl pyruvate)-treated rats (n=6). The data are presented as the mean ± SEM. *p<0.001 versus SHAM, †p<0.001 and ?p<0.01 versus NT and LR.

Mentions: For observation of the mesenteric microcirculation, single and unbranched postcapillary venules were selected; their diameters ranged from 20–25 μm in all groups. The observed leukocyte-endothelial interactions, assessed after 24 h of bacteremia, showed that treatment of the animals with REP solution significantly reduced the number of rolling leukocytes to the level observed in the sham group, whereas there was an increased number (∼2.5-fold increase) of rolling cells in the NT and LR groups. Similarly, REP solution reduced the numbers of adherent and migrated leukocytes to the levels attained in the sham group, whereas in both the NT and the LR groups, there were increased numbers of adherent leukocytes (∼3-fold increase) and migrated cells (∼3.5-fold) compared with numbers in the sham group (Figure 2). Representative photomicrographs are shown in Figure 3. Analyses of WBC counts showed that the infusion of bacteria caused leukopenia at 3 h due to a reduction in the number of lymphocytes and monocytes, followed by significant leukocytosis with granulocytosis at 24 h. Furthermore, there was an intense and progressive reduction in the number of platelets. However, no differences were observed after treatment of the animals with either the LR or the REP solution. Meanwhile, sham-operated rats exhibited transient leukocytosis with granulocytosis associated with the surgical procedure. The results are summarized in Table 1.


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

Guarda IF, Correia CJ, Breithaupt-Faloppa AC, Ferreira SG, Moreno AC, Martinez MB, Rocha-e-Silva M, Sannomiya P - Clinics (Sao Paulo) (2015)

The number of rolling (3 min), adherent (100 μm venule length) and migrated (5,000 μm2) leukocytes in the rat mesenteric microcirculation 24 h after intravenous injection of E. coli. SHAM, sham-operated rats (n=5); NT, non-treated rats (n=7); LR, lactated Ringer's solution (4 mL/kg)-treated rats (n=7); REP (4 mL/kg LR + 50 mg/kg ethyl pyruvate)-treated rats (n=6). The data are presented as the mean ± SEM. *p<0.001 versus SHAM, †p<0.001 and ?p<0.01 versus NT and LR.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496755&req=5

f2-clin_70p508: The number of rolling (3 min), adherent (100 μm venule length) and migrated (5,000 μm2) leukocytes in the rat mesenteric microcirculation 24 h after intravenous injection of E. coli. SHAM, sham-operated rats (n=5); NT, non-treated rats (n=7); LR, lactated Ringer's solution (4 mL/kg)-treated rats (n=7); REP (4 mL/kg LR + 50 mg/kg ethyl pyruvate)-treated rats (n=6). The data are presented as the mean ± SEM. *p<0.001 versus SHAM, †p<0.001 and ?p<0.01 versus NT and LR.
Mentions: For observation of the mesenteric microcirculation, single and unbranched postcapillary venules were selected; their diameters ranged from 20–25 μm in all groups. The observed leukocyte-endothelial interactions, assessed after 24 h of bacteremia, showed that treatment of the animals with REP solution significantly reduced the number of rolling leukocytes to the level observed in the sham group, whereas there was an increased number (∼2.5-fold increase) of rolling cells in the NT and LR groups. Similarly, REP solution reduced the numbers of adherent and migrated leukocytes to the levels attained in the sham group, whereas in both the NT and the LR groups, there were increased numbers of adherent leukocytes (∼3-fold increase) and migrated cells (∼3.5-fold) compared with numbers in the sham group (Figure 2). Representative photomicrographs are shown in Figure 3. Analyses of WBC counts showed that the infusion of bacteria caused leukopenia at 3 h due to a reduction in the number of lymphocytes and monocytes, followed by significant leukocytosis with granulocytosis at 24 h. Furthermore, there was an intense and progressive reduction in the number of platelets. However, no differences were observed after treatment of the animals with either the LR or the REP solution. Meanwhile, sham-operated rats exhibited transient leukocytosis with granulocytosis associated with the surgical procedure. The results are summarized in Table 1.

Bottom Line: 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.There was also an intense and progressive reduction in the number of platelets.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração do Hospital das Clínicas da Faculdade de Medicinada Universidade de São Paulo (InCor), São Paulo, SP, Brazil.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus