Endotoxin-induced acute tubular necrosis in cirrhotic rats

In order to clarify the role of endotoxin in acute tubular necrosis in liver cirrhosis, lipopolysaccharide (LPS) was injected to rats with liver injury with exposure to carbon tetrachloride (CCl4) inhalation. Rats showed liver cirrhosis with ascites retention after 10 weeks' CCl4 treatment and liver fibrosis after 6 weeks' CCl4 treatment. Histopathological grading of kidney injuries after LPS treatment was more severe either in cirrhotic rats or in liver fibrotic rats than in normal rats. All cirrhotic rats had severe acute tubular necrosis after either dose of LPS, but only small necrotic foci of tubuli were seen in a few normal and liver fibrotic rats. The results indicate that endotoxin, which overflows due to disturbance of inactivation in the cirrhotic liver, may contribute to acute tubular necrosis. This effect of endotoxin is supposed to be a direct hemodynamic damage.