The Distribution of ³H-Labeled Endotoxin in the Kidney of Liver Cirrhotic Rats

Abstract

Although the etiology and pathogenesis of progressive renal failure is largely unknown, endotoxin is supposed to be one of the contributory factors. However, the distribution of endotoxin in liver cirrhosis has not been clarified. Therefore we studied the distribution of ³H-labeled endotoxin in the kidney in rats with CCl₄-induced liver injury. Daily inhalations of CCl₄ on rats for 6 and 10 weeks produced liver fibrosis (LF group, N = 5) and cirrhosis (LC group, N = 5), respectively. At 6 or 10 weeks, animals were sacrificed 24 hours after an intravenous injection of endotoxin labeled with ³H at the galactose moiety (12,000 cpm/1 g body weight). In the liver, ³H-labeled endotoxin was taken up mainly by Kupffer cells as determined by autoradiography. Compared to control rats, in rats of the LC or LF group the measured amount of ³H-labeled endotoxin per gram kidney or ml blood increased, while that of the liver was significantly decreased. A positive correlation of the amount of ³H-labeled endotoxin per weight or volume respectively was shown between kidney and blood, but not between lung or spleen and blood. These results suggest that overflow of endotoxin due to decreased inactivation in the liver causes endotoxemia in liver injury and that the resulting endotoxemia may directly affect the kidney. The resulting endotoxin-induced vasoconstriction may be a contributory factor for the progressive renal failure frequently observed in liver cirrhosis.

Keywords:

• endotoxin
• hepato-renal syndrome
• acute tubular necrosis
• acute renal failure
• liver cirrhosis
• reticuloendothelial system