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

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.

Ethyl Pyruvate Reduces Systemic Leukocyte Activation via Caspase-1 and NF-κB After Blunt Chest Trauma and Haemorrhagic Shock

“…Thus, the data suggest, that TxT+H/R-induced systemic activation can be diminished by EtP, subsequently reducing the transmigration of neutrophils to sites of inflammation upon a traumatic insult. Moreover, in a model of E. coli -induced sepsis, treatment with EtP significantly diminished inflammation by reduced systemic leukocyte rolling, adherence and migration in the mesenteric microcirculation ( 63 ). In the present study, resuscitation with EtP reduced the expression of CD11b on circulating neutrophils, indicating at an anti-inflammatory effect via inhibition of systemic activation of leukocytes.…”

Immunocompetent host develops mild intestinal inflammation in acute infection with Toxoplasma gondii

“…The slides were mounted, and images were captured using an Olympus BX50 microscope equipped with a 3CCD Pro-series camera. The objects stained with AEC and DAB on the walls of mesenteric vessels were identified after threshold determination, and the stained area was quantified using an image analyzer (NIS-elements; Nikon, Tokyo, Japan [ 24 ].…”

Ethyl pyruvate, a versatile protector in inflammation and autoimmunity

“…Numerous studies have shown that the beneficial effects of EP in animal models of sepsis were related to its HMGB1-inhibiting activity [ 22 , 89 , 90 ]. Further, EP efficiently reduced the inflammation in the mesenteric microcirculation via downregulation of P-selectin and intercellular adhesion molecule-1 (ICAM-1) in septic rats [ 91 ]. In a cecal ligation and puncture (CLP) model of sepsis, EP was shown to reduce the mortality of rats, and it also reduced mitochondrial swelling and dysfunction, as well as the mitochondrial expression of aquaporin-8, a water channel protein that significantly contributed to mitochondrial swelling [ 92 ].…”