Urinary trypsin inhibitor suppresses excessive generation of superoxide anion radical, systemic inflammation, oxidative stress, and endothelial injury in endotoxemic rats

The protective effects of ulinastatin, a human urinary trypsin inhibitor (UTI), against superoxide radical (O (2) (-center dot) ) generation, systemic inflammation, lipid peroxidation, and endothelial injury were investigated in endotoxemic rats. Twenty-one Wistar rats were allocated to a control group, a UTI group, and a sham group. A bolus of lipopolysaccharide (LPS; 3 mu g/g) was administered intravenously to the control group, a bolus of LPS and UTI (5 U/g) to the UTI group, and a bolus of saline to the sham group. The O (2) (-center dot) generated was measured as the current in the right atrium using an electrochemical O (2) (-center dot) sensor. Plasma nitrite, high mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-alpha, inteleukin (IL)-6, malondialdehyde, and soluble intercellular adhesion molecule-1 (sICAM-1) were measured 360 min after LPS administration. The O (2) (-center dot) current increased in the control group and was significantly attenuated in the UTI group after 55 min (P < 0.05 at 55-60 min, P < 0.01 at 65-360 min). Plasma nitrite, HMGB1, TNF-alpha, IL-6, malondialdehyde, and sICAM-1 were attenuated in the UTI group. UTI suppressed excessive O (2) (-center dot) generation, systemic inflammation, lipid peroxidation, and endothelial injury in endotoxemic rats.