Protective Effects of Antioxidants and Protease Inhibitors on Endotoxin Shock and Their Scavenging Effects on Oxygen-derived Free Radicals -Experimental Investigations of the Active Oxygen Species In Vivo and In Vitro-

Jun Taguchi, Toshio Kadota, Syoetsu Tamakuma

First Department of Surgery, National Defense Medical College

The role of active oxygen species in the process of organ failure was investigated and protective effects of antioxidants and protease inhibitors against endotoxin shock were experimentally studied in rats. Experimental shock was induced by a single intravenous injection of endotoxin at a dose of 4 mg/kg. After the injection, systolic blood pressure and hepatic tissue blood flow were reduced. Furthermore neutrophil-derived superoxide and lipoperoxide levels in the liver were markedly elevated. Severe destruction of the mitochondrial structure of hepatocytes was seen. Superoxide-induced chemiluminescence from in situ liver surface was increased after endotoxin injection. On the other hand, all these changes were prevented by pretreatment with superoxide dismutase and catalase, coenzyme Q₁₀, solcoseryl, nafamostat mesilate, and ulinastatin. These results indicate that active oxygen species, such as superoxide and hydrogen peroxide, are involved in the pathogenesis of organ failure following endotoxin shock, and suggest that antioxidants and protease inhibitors may exert some protective effects against organ failure in endotoxin shock.

Key words
endotoxin shock, active oxygen, antioxidant, protease inhibitor

Reprint requests
Jun Taguchi Self Defense Force Etajima Hospital
737-21 Etajima-cho, Aki-gun, Hiroshima JAPAN

Accepted
June 17, 1992

To read the PDF file you will need Abobe Reader installed on your computer.