Mehendale H M, El-Bassiouni E A
Drug Metab Dispos. 1975 Nov-Dec;3(6):543-56.
The uptake, metabolism, and release of aldrin and dieldrin by the lungs were studied by use of isolated perfused rabbit lungs that were artificially ventilated and perfused through the pulmonary artery. Both recirculating and single-pass experiments were conducted using an artificial medium as perfusate. Aldrin accumulated in the lung from the perfusate through two distinct phases of uptake: a rapid phase involving simple diffusion and nonspecific binding and a slower phase representing its metabolic turnover as dieldrin. Dieldrin was not metabolized but accumulated in the lungs by a saturable and a nonsaturable process. Single-pass experiments with aldrin indicated that the initial velocity of uptake could be fitted to one component and a constant representing the rate of metabolism. Uptake of dieldrin was biphasic: one phase independent of the perfusate concentration and the other saturable with respect to the perfusate concentration. By the application of Michaelis-Menten kinetics, the maximum amount of dieldrin accumulation attributable to the saturable component was calculated to be 0.64 mumol/lung. Our results indicate that the accumulation of these chlorinated xenobiotics takes place through the processes of simple diffusion followed by nonspecific tissue binding. There was no evidence for irreversible binding of aldrin or dieldrin, its epoxide, in the lung. While the lung plays a role in metabolizing aldrin to dieldrin followed by a transient storage, neither substrate has the potential for long-term storage in the lung.
利用通过肺动脉进行人工通气和灌注的离体灌注兔肺,研究了艾氏剂和狄氏剂在肺中的摄取、代谢和释放。使用人工培养基作为灌注液进行了循环和单次通过实验。艾氏剂通过两个不同的摄取阶段从灌注液中在肺中积累:一个快速阶段涉及简单扩散和非特异性结合,另一个较慢阶段代表其作为狄氏剂的代谢周转。狄氏剂未被代谢,而是通过一个可饱和和一个不饱和过程在肺中积累。用艾氏剂进行的单次通过实验表明,摄取的初始速度可以拟合为一个成分和一个代表代谢速率的常数。狄氏剂的摄取呈双相性:一个阶段与灌注液浓度无关,另一个阶段相对于灌注液浓度是可饱和的。通过应用米氏动力学,计算出可饱和成分导致的狄氏剂最大积累量为0.64 μmol/肺。我们的结果表明,这些氯化外源性物质的积累是通过简单扩散然后非特异性组织结合的过程发生的。没有证据表明艾氏剂或其环氧化物狄氏剂在肺中存在不可逆结合。虽然肺在将艾氏剂代谢为狄氏剂并随后进行短暂储存方面发挥作用,但两种底物都没有在肺中长期储存的潜力。