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补充牛磺酸对肠外营养相关肝脂肪变性及利多卡因代谢的影响。一项采用大鼠离体肝脏灌注的研究。

Effects of taurine supplementation in parenteral nutrition-associated hepatosteatosis and lidocaine metabolism. A study using isolated rat liver perfusion.

作者信息

Zaman N, Tam Y K, Jewell L D, Coutts R T

机构信息

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.

出版信息

Drug Metab Dispos. 1996 May;24(5):534-41.

PMID:8723733
Abstract

The effects of taurine in parenteral nutrition (PN)-related hepatic dysfunction are controversial. The aims of the present study were to evaluate the effects of taurine on hepatic function and on lidocaine metabolism, using two strengths of taurine (15 and 50 mg/dl) that are present in commercially available preparations. Animals (N > or = 4) were randomly assigned to one of the four 7-day treatment groups: chow-fed (CF); dextrose/amino acids (PN); dextrose/amino acids and taurine, 15 mg/dl (T15); dextrose/amino acids and taurine, 50 mg/dl (T50). Between 40-75% of the animals treated with PN developed steatosis. The origin of steatosis was zonal specific and dependent on taurine treatment. All livers in the CF group had a normal cellular architecture. Lidocaine metabolism was found to be impaired in groups PN, T15, and T50. This was indicated by a significant reduction in the intrinsic clearance values: 70%, 76%, and 85% in groups PN, T15, and T50, respectively (p < 0.05). Metabolites-to-drug ratios indicated that N-dealkylation, m-hydroxylation, and aryl methyl hydroxylation were significantly reduced in all treatment groups; the most pronounced effect was observed in the T50 group. These findings suggest that PN infusion results in impaired liver function, and the reduction of drug elimination rate is exacerbated by the addition of taurine.

摘要

牛磺酸在肠外营养(PN)相关肝功能障碍中的作用存在争议。本研究的目的是使用市售制剂中存在的两种浓度的牛磺酸(15和50mg/dl),评估牛磺酸对肝功能和利多卡因代谢的影响。将动物(N≥4)随机分配到四个为期7天的治疗组之一:正常饮食(CF);葡萄糖/氨基酸(PN);葡萄糖/氨基酸加15mg/dl牛磺酸(T15);葡萄糖/氨基酸加50mg/dl牛磺酸(T50)。接受PN治疗的动物中有40-75%出现了脂肪变性。脂肪变性的起源具有区域特异性且依赖于牛磺酸治疗。CF组所有肝脏的细胞结构均正常。发现PN组、T15组和T50组的利多卡因代谢受损。这表现为内在清除率值显著降低:PN组、T15组和T50组分别降低了70%、76%和85%(p<0.05)。代谢物与药物的比率表明,所有治疗组的N-脱烷基化、间位羟基化和芳基甲基羟基化均显著降低;在T50组观察到最明显的效果。这些发现表明,PN输注会导致肝功能受损,并且添加牛磺酸会加剧药物消除率的降低。

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