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


METHODS
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.
Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Ube, Yamaguchi, Japan.
Ryo
R
Tanaka
Motoki
M
Fujita
Ryosuke
R
Tsuruta
Kenji
K
Fujimoto
Hiromi Shinagawa
HS
Aki
Kazumi
K
Kumagai
Tetsuya
T
Aoki
Akihiro
A
Kobayashi
Tomonori
T
Izumi
Shunji
S
Kasaoka
Makoto
M
Yuasa
Tsuyoshi
T
Maekawa
D000818:Animals; D004727:Endothelium / Q000187:drug effects / Q000473:pathology; D019446:Endotoxemia / Q000097:blood / Q000276:immunology / Q000473:pathology; D006023:Glycoproteins / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000097:blood / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D019344:Lactic Acid / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism*; D014361:Trypsin Inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
D006023:Glycoproteins; D024243:HMGB1 Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014361:Trypsin Inhibitors; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; D019344:Lactic Acid; D008315:Malondialdehyde; C028665:urinastatin