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
- Univ. of Minnesota, Minneapolis
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
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Related Subjects
550900 -- Pathology
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
BODY
DIGESTIVE SYSTEM
DIGESTIVE SYSTEM DISEASES
DISEASES
ELECTRON MICROSCOPY
GLANDS
HEMOLYSIS
LIVER
LIVER CIRRHOSIS
LYSIS
MAMMALS
METABOLISM
MICROSCOPY
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PATIENTS
RATS
RODENTS
SULFONIC ACIDS
TAURINE
VERTEBRATES