Duane P, Raja K B, Simpson R J, Peters T J
Division of Clinical Cell Biology, MRC Clinical Research Centre, Harrow, Middlesex, U.K.
Alcohol Alcohol. 1992 Sep;27(5):539-44.
Chronic alcohol misusers frequently accumulate significant amounts of excess iron, but the mechanism of this loading is unknown. In vivo whole-body retention studies demonstrated, on average, a two-fold increase in intestinal iron absorption in six male chronic alcoholics. Degrees of iron loading as assessed by serum ferritin or hepatic iron levels did not correlate with alcohol consumption or liver function tests. In vitro studies of iron uptake at varying medium iron concentrations by duodenal mucosa biopsies showed increased iron uptake by tissue from the chronic alcoholics, particularly at the highest medium iron concentration used. Analysis of the uptake data showed similar Michaelis-Menten kinetic constants for uptake by tissue from control subjects and alcoholics. The analysis showed, in addition, a linear component for 59Fe uptake. This component was five-fold greater for the tissue from the chronic alcoholics compared to the controls at the highest medium iron concentration. 57Co-cyanocobalamin was included in the incubation medium as a tissue extracellular fluid marker (ECF). It was found that the apparent distribution volume of the ECF marker, reflecting tissue permeability, was 75% higher for the biopsies from the alcoholics compared to control subjects. These results, together with the previous reports of enhanced in vitro and in vivo intestinal permeability to 51Cr-EDTA in chronic alcoholics, indicate that unregulated increased iron absorption via the non-carrier-mediated paracellular route contributes to the iron overload in chronic alcoholics.
慢性酒精滥用者常常会蓄积大量多余的铁,但这种铁负荷的机制尚不清楚。体内全身铁潴留研究表明,六名男性慢性酒精中毒者的肠道铁吸收平均增加了两倍。通过血清铁蛋白或肝脏铁水平评估的铁负荷程度与酒精摄入量或肝功能检查无关。在不同培养基铁浓度下对十二指肠黏膜活检组织进行铁摄取的体外研究表明,慢性酒精中毒者组织的铁摄取增加,尤其是在所用的最高培养基铁浓度下。对摄取数据的分析显示,对照组和酒精中毒者组织摄取的米氏动力学常数相似。此外,分析还显示59Fe摄取存在线性成分。在最高培养基铁浓度下,慢性酒精中毒者组织的该成分比对照组大五倍。孵育培养基中加入了57Co-钴胺素作为组织细胞外液标记物(ECF)。结果发现,反映组织通透性的ECF标记物的表观分布容积,酒精中毒者活检组织比对照组高75%。这些结果,连同之前关于慢性酒精中毒者体外和体内肠道对51Cr-EDTA通透性增强的报道,表明通过非载体介导的细胞旁途径无调节地增加铁吸收导致了慢性酒精中毒者的铁过载。