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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

Quantitative evaluation of P-selectin and ICAM-1 expression on rat mesenteric microvessels 24 h after intravenous injection of E. coli. SHAM, sham-operated rats; NT, non-treated rats; LR, lactated Ringer's solution (4 mL/kg)-treated rats; REP (4 mL/Kg LR + 50 mg/kg ethyl pyruvate)-treated rats. The presented values are the mean ± SEM for 3 samples/rat, with 3 rats/group. The analyses were performed using NIS-Elements BR software (Nikon). The results are presented as objectsx103/μm2. *p<0.001 versus SHAM, §p<0.01 versus SHAM and NT, †p<0.001 versus NT, ?p<0.01 versus LR.
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f4-clin_70p508: Quantitative evaluation of P-selectin and ICAM-1 expression on rat mesenteric microvessels 24 h after intravenous injection of E. coli. SHAM, sham-operated rats; NT, non-treated rats; LR, lactated Ringer's solution (4 mL/kg)-treated rats; REP (4 mL/Kg LR + 50 mg/kg ethyl pyruvate)-treated rats. The presented values are the mean ± SEM for 3 samples/rat, with 3 rats/group. The analyses were performed using NIS-Elements BR software (Nikon). The results are presented as objectsx103/μm2. *p<0.001 versus SHAM, §p<0.01 versus SHAM and NT, †p<0.001 versus NT, ?p<0.01 versus LR.

Mentions: As illustrated in Figure 4, the expression of P-selectin and ICAM-1 on mesenteric microvessels was significantly increased in the NT group compared with the sham group. Treatment of the animals with REP solution reduced the expression of both adhesion molecules (P-selectin and ICAM-1) to the levels attained in the sham group. In contrast, treatment with LR partially reduced P-selectin expression but did not modify ICAM-1 expression on mesenteric microvessels.


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)

Quantitative evaluation of P-selectin and ICAM-1 expression on rat mesenteric microvessels 24 h after intravenous injection of E. coli. SHAM, sham-operated rats; NT, non-treated rats; LR, lactated Ringer's solution (4 mL/kg)-treated rats; REP (4 mL/Kg LR + 50 mg/kg ethyl pyruvate)-treated rats. The presented values are the mean ± SEM for 3 samples/rat, with 3 rats/group. The analyses were performed using NIS-Elements BR software (Nikon). The results are presented as objectsx103/μm2. *p<0.001 versus SHAM, §p<0.01 versus SHAM and NT, †p<0.001 versus NT, ?p<0.01 versus LR.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-clin_70p508: Quantitative evaluation of P-selectin and ICAM-1 expression on rat mesenteric microvessels 24 h after intravenous injection of E. coli. SHAM, sham-operated rats; NT, non-treated rats; LR, lactated Ringer's solution (4 mL/kg)-treated rats; REP (4 mL/Kg LR + 50 mg/kg ethyl pyruvate)-treated rats. The presented values are the mean ± SEM for 3 samples/rat, with 3 rats/group. The analyses were performed using NIS-Elements BR software (Nikon). The results are presented as objectsx103/μm2. *p<0.001 versus SHAM, §p<0.01 versus SHAM and NT, †p<0.001 versus NT, ?p<0.01 versus LR.
Mentions: As illustrated in Figure 4, the expression of P-selectin and ICAM-1 on mesenteric microvessels was significantly increased in the NT group compared with the sham group. Treatment of the animals with REP solution reduced the expression of both adhesion molecules (P-selectin and ICAM-1) to the levels attained in the sham group. In contrast, treatment with LR partially reduced P-selectin expression but did not modify ICAM-1 expression on mesenteric microvessels.

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