Hepatic lesions and hemolysis following administration of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oyl taurine to rats.
Patients with a metabolic block in the conversion of THCA 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. In the present study, 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 micronmol/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 X 10(-4) M. Liver biopsy sections from rats infused for a 2 hr period with tauro-THCA were examined by electron microscopy and showed dilation of the rough endoplasmic reticulum and distortion of mitochondrial membranes. Cholestasis was not induced, since tauro-THCA actually caused a greater choleretic response for a given rate of bile salt excretion than did taurocholate. This study raises the possibility that the clinical liver disease seen in patients with a metabolic block in the conversion of THCA into cholic acid may be caused by tauro-THCA.
D000743:Anemia, Hemolytic / Q000139:chemically induced* / Q000209:etiology; D000818:Animals; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002793:Cholic Acids / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects; D005260:Female; D006456:Hemoglobinuria / Q000139:chemically induced; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000209:etiology; D008930:Mitochondria, Liver / Q000187:drug effects; D051381:Rats; D013654:Taurine / Q000378:metabolism; D013656:Taurocholic Acid / Q000009:adverse effects / Q000378:metabolism
D001647:Bile Acids and Salts; D002793:Cholic Acids; D013654:Taurine; D013656:Taurocholic Acid