1. Urinary trypsin inhibitor suppresses excessive generation of superoxide anion radical, systemic inflammation, oxidative stress, and endothelial injury in endotoxemic rats.
- Author
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Tanaka R, Fujita M, Tsuruta R, Fujimoto K, Aki HS, Kumagai K, Aoki T, Kobayashi A, Izumi T, Kasaoka S, Yuasa M, and Maekawa T
- Subjects
- Animals, HMGB1 Protein blood, HMGB1 Protein immunology, Humans, Inflammation blood, Inflammation chemically induced, Intercellular Adhesion Molecule-1 blood, Intercellular Adhesion Molecule-1 immunology, Interleukin-6 blood, Interleukin-6 immunology, Lactic Acid blood, Lipopolysaccharides immunology, Lipopolysaccharides pharmacology, Male, Malondialdehyde blood, Malondialdehyde immunology, Rats, Rats, Wistar, Tumor Necrosis Factor-alpha blood, Tumor Necrosis Factor-alpha immunology, Endothelium drug effects, Endothelium pathology, Endotoxemia blood, Endotoxemia immunology, Endotoxemia pathology, Glycoproteins pharmacology, Inflammation immunology, Oxidative Stress drug effects, Superoxides metabolism, Trypsin Inhibitors pharmacology
- Abstract
Objective and Design: The protective effects of ulinastatin, a human urinary trypsin inhibitor (UTI), against superoxide radical (O(2)(-*)) generation, systemic inflammation, lipid peroxidation, and endothelial injury were investigated in endotoxemic rats., Materials and Treatment: Twenty-one Wistar rats were allocated to a control group, a UTI group, and a sham group. A bolus of lipopolysaccharide (LPS; 3 microg/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., Methods: The O(2)(-*) generated was measured as the current in the right atrium using an electrochemical O(2)(-*) sensor. Plasma nitrite, high mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, malondialdehyde, and soluble intercellular adhesion molecule-1 (sICAM-1) were measured 360 min after LPS administration., Results: The O(2)(-*) 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., Conclusions: UTI suppressed excessive O(2)(-*) generation, systemic inflammation, lipid peroxidation, and endothelial injury in endotoxemic rats.
- Published
- 2010
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