EFFECTS OF URINASTATIN AND FREE-RADICAL SCAVENGERS ON HEPATIC LIPID-PEROXIDATION IN ENDOTOXEMIA

In gram-negative septicemia, endotoxin-induced free radicals probably damage the liver cells by membrane lipid peroxidation. Phosphotidylcho line hydroperoxide (PCOOH), a primary Lipid peroxidation product can b e applied as a parameter to measure the extent of liver damage. The pr otective effects of urinastatin and free radical scavengers, superoxid e dismutase (SOD), and catalase against hepatic lipid peroxidation and tissue energy reserves in the liver during endotoxemia were evaluated in rats with gram-negative septicemia induced by cecal ligation and p uncture (CLP). One hundred and sixty-five rats were divided into three groups. The first two groups consisted of 45 rats each. Group (1) was used for blood endotoxin level and liver function tests, group (2) fo r hepatic energy charge and PCOOH measurement, and group (3) (n = 75) for survival study. In each group, control animals received saline inj ection only, Urinastatin was injected twice intravenously through tail veins using 50,000 u/kg at 0 and 12 hr after CLP. SOD 90,000 u/kg and catalase 50,000 u/kg were given subcutaneously just before CLP and ev ery 3 hr thereafter up to 24 hr. Liver and blood specimens were taken at time points 0, 12, and 24 hr after CLP. Increased concentration of PCOOH in liver denotes that endotoxemia can damage the liver by hepato cellular lipid peroxidation. Attenuation of lipid peroxidation, which correlated with liver enzyme leakage, was noted by finding significant decreased concentrations of PCOOH (P < 0.001), improvement in energy charge (P < 0.05), and survivability (P < 0.05) was seen in urinastati n or radical scavenger-treated groups. These results suggested that ur inastatin has protective effect against free radical-induced lipid per oxidation probably by inhibiting proteases especially elastase, from p olymorphonuclear leucocytes. SOD and catalase, which scavenged oxygen free radicals, also suppressed free radical-induced lipid peroxidation . Improvement in survivability was also seen in treated groups. (C) 19 96 Academic Press, Inc.