Mollière M, Foth H, Kahl R, Kahl G F
Toxicology. 1987 Aug;45(2):143-54. doi: 10.1016/0300-483x(87)90100-4.
The influence of the insertion of a liver into the perfusion circuit of a lung on the availability of benzo[a]pyrene and benzo[a]pyrene metabolites to the lung was examined. Perfused lungs from 5,6-benzoflavone pretreated rats release high quantities of free benzo[a]pyrene metabolites and conjugates into the perfusion medium. The insertion of a liver taken from an untreated rat reduces the concentration of unmetabolized substrate and of free diol, quinone and phenol metabolites to less than 20% of the concentrations found in the absence of the liver. When the liver of a 5,6-benzoflavone-pretreated rat is used, substrate depletion is not much greater than in the experiments with control livers; however, the concentration of free metabolites is further reduced to one third. In lung tissue, only very low levels of benzo[a]pyrene and greatly reduced levels of free and conjugated metabolites are found when a 5,6-benzoflavone-induced liver had been present during perfusion. These findings can explain the protective effect of the liver on covalent binding of benzo[a]pyrene metabolites to pulmonary macro-molecules observed in previous experiments with the combined liver-lung perfusion model [Klaus et al., Biochem. Biophys. Res. Commun., 105 (1982) 596].
研究了将肝脏插入肺灌注回路对肺中苯并[a]芘及其代谢产物可用性的影响。来自经5,6-苯并黄酮预处理大鼠的灌注肺会向灌注介质中释放大量游离的苯并[a]芘代谢产物和结合物。插入取自未处理大鼠的肝脏后，未代谢底物以及游离二醇、醌和酚类代谢产物的浓度降低至无肝脏时所测浓度的20%以下。当使用经5,6-苯并黄酮预处理大鼠的肝脏时，底物消耗并不比使用对照肝脏的实验大很多；然而，游离代谢产物的浓度进一步降低至三分之一。在肺组织中，当灌注过程中存在经5,6-苯并黄酮诱导的肝脏时，仅能检测到极低水平的苯并[a]芘以及大幅降低的游离和结合代谢产物水平。这些发现可以解释在先前联合肝肺灌注模型实验中观察到的肝脏对苯并[a]芘代谢产物与肺大分子共价结合的保护作用[克劳斯等人，《生物化学与生物物理研究通讯》，105(1982)596]。
