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KMID : 0616619960020020117
Journal of Soonchunhyang Medical College
1996 Volume.2 No. 2 p.117 ~ p.129
A Study of Hepatic Injury Induced by Endotoxin in Rats


Abstract
To study the mechanism of endotoxin-induced hepatocelluar injury in rats, a single dose of endotoxin, 15mg/kg, was injected intraperitoneally with or without dexamethasone pretreatment. Studies induced light microscopic, histochemical, and electronmicroscopic observations with concomitant assay of free acid phosphatase activity of liver homogenates. The results showed an increase of acid phosphatase activity as early as 30 minutes after the injection of endotoxin, and by light microscopy random focal necrosis of liver cells at 1 hour and fibrin thrombi formation in sinusoids especially within the area of necrosis at 3 hours. However, ultrastructural alteration was noted as early as 5 minutes after the injection of endotoxin characterized by marked dilatation of the RER. The degrees of necrosis, fibrin thrombus formation, and elevation of free acid phosphatase activity in the liver homogenates seemed to parallel each other suggesting a possible interrelationship among these phenomena. However, the ultrastructural changes of the hepatocytes were present far ahead of the appearance of fibrin thrombi formation. Therefore, the causal relationship of the fibrin thrombi to liver cell injury appeared unlikely. Despite the increase of free acid phosphatase activity in liver homogenates,no demonstrable structural disruption of lysosomal membrane was noted. In view of the prominent changes of RER 5 minutes after the endotoxin administration, the primary injurious effect of endotoxin affects the membrane system of all organelles including the lysosomal membrane, leading to the leakage of lysosomal enzymes into the cytoplasmic sap. Dexamethasone pretreatment alleviated necrosis and markedly inhibited fibrin thrombus formation, and the mechanism of this effect is considered to be a stabilizing effect of glucocorticoid upon membrane systems.
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