T. Htwe et al., EFFECTS OF URINASTATIN AND FREE-RADICAL SCAVENGERS ON HEPATIC LIPID-PEROXIDATION IN ENDOTOXEMIA, The Journal of surgical research, 61(1), 1996, pp. 206-214
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.