Geubel A P, Mairlot M C, Buchet J P, Dive C, Lauwerys R
Department of Gastroenterology, St-Luc University Hospital, Catholic University of Louvain, Brussels, Belgium.
Int J Clin Pharmacol Res. 1988;8(2):117-22.
To investigate the influence of liver cirrhosis on the capacity of methylation, the urinary excretion of the methylated forms of arsenic was measured by atomic absorption spectrometry after the administration of a small dose of inorganic arsenic. The study was carried out in 13 normal controls, 18 patients with various clinical conditions, but without evidence of parenchymal liver disease, and 38 with cirrhosis of varied aetiology and severity. In normal controls, the percentage of arsenic excreted as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) averaged 12.3 +/- 2.8% and 23.3 +/- 6.4%, respectively, and was not significantly different from that obtained in disease controls. The presence of liver cirrhosis did not affect the percentage of the injected dose excreted within 24 h. However, cirrhotic patients excreted significantly less MMA (4.7 +/- 3.3, p less than 0.001) and more DMA (40.4 +/- 16.6%, p less than 0.001). The amount of MMA correlated with the 14C aminopyrine breath test (r = 0.43) and was invariably lower than the normal range in patients with severe liver disease. These findings indicate that liver cirrhosis is associated with profound abnormalities of the methylation pathway, which might have potential consequences in the metabolism of endogenous amines and xenobiotics.
为研究肝硬化对甲基化能力的影响，在给予小剂量无机砷后，采用原子吸收光谱法测定砷甲基化形式的尿排泄量。该研究纳入了13名正常对照者、18名患有各种临床疾病但无实质性肝脏疾病证据的患者以及38名不同病因和严重程度的肝硬化患者。在正常对照者中，以一甲基砷酸（MMA）和二甲基砷酸（DMA）形式排泄的砷的百分比平均分别为12.3±2.8%和23.3±6.4%，与疾病对照组获得的结果无显著差异。肝硬化的存在并不影响24小时内排泄的注射剂量的百分比。然而，肝硬化患者排泄的MMA明显减少（4.7±3.3，p<0.001），而DMA增多（40.4±16.6%，p<0.001）。MMA的量与14C氨基比林呼气试验相关（r = 0.43），并且在严重肝病患者中始终低于正常范围。这些发现表明，肝硬化与甲基化途径的严重异常有关，这可能对内源性胺类和外源性物质的代谢产生潜在影响。
