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

Journal Article · · J. Lab. Clin. Med.; (United States)
OSTI ID:7091199

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 ..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 x 10/sup -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.

OSTI ID:
7091199
Journal Information:
J. Lab. Clin. Med.; (United States), Journal Name: J. Lab. Clin. Med.; (United States) Vol. 90:3; ISSN JLCMA
Country of Publication:
United States
Language:
English