HEPATIC LESIONS AND HEMOLYSIS FOLLOWING ADMINISTRATION OF 3-ALPHA, 7-ALPHA, 12-ALPHA-TRIHYDROXY-5-BETA-CHOLESTAN-26-OYL TAURINE TO RATS

  • 1 January 1977
    • journal article
    • research article
    • Vol. 90  (3) , 536-548
Abstract
Patients with a metabolic block in the conversion of THCA [3.alpha., 7.alpha., 12.alpha.-trihydroxy-5.beta.-cholestan-26-oyl taurine] into cholic acid develop cirrhosis and hemolysis and die of hepatic failure. In these patients, THCA is largely conjugated to taurine (tauro-THCA) and excreted instead of being converted into cholic acid. The effects of tauro-THCA on hemolysis, bile flow and hepatic morphology were evaluated in bile fistula rats. All rats infused with tauro-THCA at rates of 0.25, 0.50 or 0.75 .mu.mol/min developed hemolysis with hemoglobinuria. A direct toxic effect of tauro-THCA on washed human red blood cell membranes was demonstrated at a concentration of 8 .times. 10-4 M. Liver biopsy sections from rats infused for a 2 h period with tauro-THCA were examined by EM and showed dilation of the rough endoplasmic reticulum and distortion of mitochondrial membranes. Cholestasis was not induced, since tauro-THCA acutally caused a greater choleretic response for a given rate of bile salt excretion than did taurocholate. Clinical liver disease seen in patients with a metabolic block in the conversion of THCA into cholic acid may be caused by tauro-THCA.

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