Hepatic lesions and hemolysis following administration of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oyl taurine to rats.

Abstract

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.

• Authors: R F Hanson, G C Williams, D Hachey, H L Sharp
• Journal: The Journal of laboratory and clinical medicine (J Lab Clin Med) Vol. 90 Issue 3 Pg. 536-48 (Sep 1977) ISSN: 0022-2143 [Print] United States
• PMID: 894105 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Bile Acids and Salts
• Cholic Acids
• Taurine
• Taurocholic Acid

Topics

• Anemia, Hemolytic (chemically induced, etiology)
• Animals
• Bile (metabolism)
• Bile Acids and Salts (metabolism)
• Cholic Acids (metabolism)
• Endoplasmic Reticulum (drug effects)
• Female
• Hemoglobinuria (chemically induced)
• Humans
• Liver (drug effects, ultrastructure)
• Liver Cirrhosis (chemically induced, etiology)
• Mitochondria, Liver (drug effects)
• Rats
• Taurine (metabolism)
• Taurocholic Acid (adverse effects, metabolism)