Hanson R F, Williams G C, Hachey D, Sharp H L
J Lab Clin Med. 1977 Sep;90(3):536-48.
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.
在将四氢胆酸（THCA）转化为胆酸过程中存在代谢障碍的患者会发展为肝硬化和溶血，并死于肝衰竭。在这些患者中，THCA主要与牛磺酸结合（牛磺四氢胆酸）并排出，而不是转化为胆酸。在本研究中，在胆瘘大鼠中评估了牛磺四氢胆酸对溶血、胆汁流量和肝脏形态的影响。所有以0.25、0.50或0.75微摩尔/分钟的速率输注牛磺四氢胆酸的大鼠均出现溶血并伴有血红蛋白尿。在浓度为8×10⁻⁴ M时，证明了牛磺四氢胆酸对洗涤后的人红细胞膜有直接毒性作用。对输注牛磺四氢胆酸2小时的大鼠进行肝活检切片，通过电子显微镜检查发现粗面内质网扩张和线粒体膜变形。未诱导胆汁淤积，因为对于给定的胆盐排泄速率，牛磺四氢胆酸实际上比牛磺胆酸盐引起更大的利胆反应。这项研究提出了一种可能性，即在将THCA转化为胆酸过程中存在代谢障碍的患者中出现的临床肝病可能是由牛磺四氢胆酸引起的。
