Attili A F, Angelico M, Cantafora A, Alvaro D, Capocaccia L
Med Hypotheses. 1986 Jan;19(1):57-69. doi: 10.1016/0306-9877(86)90137-4.
Hypertransaminasemia is a frequent side effect during chenodeoxycholic administration for gallstone dissolution. Evidence suggests that this effect is not mediated by lithocholic acid, the intestinal metabolite of chenodeoxycholic acid, but that toxicity is due to the chenodeoxycholic acid itself. In vitro cytotoxicity of bile salts is positively proportional to their detergent effect, which is, on the other hand, related to their hydrophobic-hydrophilic balance. We hypothesize that in vivo also liver injury can occur when the liver is perfused by an high proportion of strongly detergent bile salts. The more detergent bile salts are unconjugated or glycine conjugated, while the lesser are taurine conjugated and sulfated. Within each class the following order of decreasing detergent power can be indicated: lithocholic greater than deoxycholic greater than chenodeoxycholic greater than cholic greater than ursodeoxycholic acid. Besides chronic exogenous administration of chenodeoxycholic or deoxycholic acids, conditions in which the liver is perfused by an high mass of highly detergent bile salts are those characterized by an enhanced intestinal biodegradation of bile salts. These conditions, which are common features of some chronic inflammatory bowel diseases, are frequently associated with liver damage. On the other hand, a normally detergent bile salt pool can become hepatotoxic for liver cells which have already been injured. In this respect, as already reported for increased sulfation, the increased proportion of taurine conjugates and the reduced formation of deoxycholic acid in liver cirrhosis can be regarded as protective mechanisms. Liver toxicity induced by bile salts' detergent action can be prevented by favouring tauroconjugation or reducing the intestinal degradation of bile salts or by administering poorly detergent bile salts.
高转氨酶血症是鹅去氧胆酸用于溶解胆结石过程中常见的副作用。有证据表明，这种效应不是由鹅去氧胆酸的肠道代谢产物石胆酸介导的，而是毒性归因于鹅去氧胆酸本身。胆汁盐的体外细胞毒性与其去污剂效应呈正相关，而去污剂效应另一方面又与其疏水-亲水平衡有关。我们推测，在体内，当肝脏被高比例的强去污剂胆汁盐灌注时，也会发生肝损伤。去污剂作用越强的胆汁盐，未结合或与甘氨酸结合的比例越高，而与牛磺酸结合和硫酸化的比例越低。在每一类中，可以指出以下去污剂能力递减的顺序：石胆酸大于脱氧胆酸大于鹅去氧胆酸大于胆酸大于熊去氧胆酸。除了长期外源性给予鹅去氧胆酸或脱氧胆酸外，肝脏被大量高去污剂胆汁盐灌注的情况是那些以胆汁盐肠道生物降解增强为特征的情况。这些情况是一些慢性炎症性肠病的常见特征，常与肝损伤相关。另一方面，正常的去污剂胆汁盐池对已经受损的肝细胞可能变得具有肝毒性。在这方面，正如已经报道的硫酸化增加一样，肝硬化中牛磺酸结合物比例的增加和脱氧胆酸形成的减少可被视为保护机制。胆汁盐去污剂作用诱导的肝毒性可以通过促进牛磺酸结合、减少胆汁盐的肠道降解或给予去污剂作用弱的胆汁盐来预防。
