Sánchez Pozzi E J, Catania V A, Luquita M G, Roma M G, Rodríguez Garay E A, Mottino A D
Instituto de Fisiología Experimental, Universidad Nacional de Rosario, Facultad de Ciencias Bioquímicas y Farmacéuticas, Argentina.
Can J Physiol Pharmacol. 1994 Nov;72(11):1265-71. doi: 10.1139/y94-181.
The effect of oral administration of the bile acid ursodeoxycholic acid on rat hepatic and intestinal microsomal UDP-glucuronosyltransferase was studied. The bile acid was administered during 8 days at a daily dose of 500 mg/kg body weight. Enzyme activity was assessed in native and activated microsomes, using bilirubin and p-nitrophenol as substrates. Activation was achieved either by including UDP-N-acetylglucosamine in the incubation mixture or by preincubating native microsomes with an optimal concentration of Lubrol Px. Irrespective of activation status of the microsomes, ursodeoxycholic acid treatment increased enzyme activities toward both substrates in intestine, but not in liver. The analysis of the degree of activation by Lubrol Px revealed that, at least for bilirubin, ursodeoxycholic acid decreased the latency of the intestinal enzyme. The analysis of the lipid composition of microsomes showed several changes in response to ursodeoxycholic acid in intestine but not in liver. Thus, a decrease in cholesterol/phospholipid ratio and an increase in the unsaturation index of total-lipid fatty acids, which correlated well with a membrane "fluidification," were observed. These modifications appear to be related to the lower latency of bilirubin UDP-glucuronosyltransferase in intestine from treated rats and could be responsible, at least in part, for the improvement of enzyme activity in this group. Whatever the mechanism involved, the increment of intestinal UDP-glucuronosyltransferase activities toward both substrates may be relevant as a complement to the hepatic enzymes in those liver diseases in which ursodeoxycholic acid is used as a therapeutic agent.
研究了口服胆汁酸熊去氧胆酸对大鼠肝脏和肠道微粒体UDP-葡萄糖醛酸基转移酶的影响。以500mg/kg体重的日剂量连续8天给予胆汁酸。使用胆红素和对硝基苯酚作为底物，在天然和活化微粒体中评估酶活性。通过在孵育混合物中加入UDP-N-乙酰葡糖胺或用最佳浓度的Lubrol Px预孵育天然微粒体来实现活化。无论微粒体的活化状态如何，熊去氧胆酸处理均增加了肠道中两种底物的酶活性，但肝脏中未增加。对Lubrol Px活化程度的分析表明，至少对于胆红素，熊去氧胆酸降低了肠道酶的潜伏时间。对微粒体脂质组成的分析表明，肠道中对熊去氧胆酸有几种变化，而肝脏中没有。因此，观察到胆固醇/磷脂比率降低和总脂质脂肪酸不饱和度指数增加，这与膜“液化”密切相关。这些修饰似乎与处理大鼠肠道中胆红素UDP-葡萄糖醛酸基转移酶的较低潜伏时间有关，并且至少部分地可能是该组中酶活性改善的原因。无论涉及何种机制，肠道UDP-葡萄糖醛酸基转移酶对两种底物的活性增加在那些将熊去氧胆酸用作治疗剂的肝脏疾病中作为肝脏酶的补充可能是相关的。
