Kotal P, Jirsa M, Kaláb M, Cervinka J, Martásek P, Kordac V
Sb Lek. 1989 Apr;91(4):113-22.
A new model for experimental studies of substances influencing porphyrin metabolism has been created. The model is formed by yeast Saccharomyces cerevisiae (RIBM-75) grown semiaerobically. The main advantages of this model include simple evocation of porphyria (intracellular accumulation of porphyrins in semiaerobic conditions) and direct measurement of experimental values (intracellular and extracellular concentrations of porphyrins). The porphyrinostatic effects of drugs can be assessed on the basis of sum of experimental values. The ratio of experimental criteria enables us to compare the influence of drugs on porphyrin permeation across the cellular membrane. Antimalarials, chloroquine and pyrimethamine, used or tested for therapy of chronic liver porphyria, have been tested on the model. The experiments showed that both chloroquine and pyrimethamine inhibited porphyrin synthesis. This effect can represent the proper therapeutical action of both drugs, which has not been known so far. Chloroquine releases the intracellular porphyrins in yeast similarly as it does in hepatocytes. However, pyrimethamine causes intracellular accumulation of porphyrins booth in yeast and hepatocytes.
已建立一种用于研究影响卟啉代谢物质的实验模型。该模型由半需氧培养的酿酒酵母（RIBM - 75）构成。此模型的主要优点包括卟啉症的简单诱发（半需氧条件下细胞内卟啉的积累）以及实验值的直接测量（卟啉的细胞内和细胞外浓度）。药物的卟啉稳定作用可根据实验值总和进行评估。实验标准的比率使我们能够比较药物对卟啉跨细胞膜渗透的影响。已在该模型上测试了用于慢性肝卟啉症治疗或正在进行测试的抗疟药氯喹和乙胺嘧啶。实验表明，氯喹和乙胺嘧啶均抑制卟啉合成。这种作用可能代表了这两种药物迄今未知的正确治疗作用。氯喹在酵母中释放细胞内卟啉的方式与在肝细胞中相同。然而，乙胺嘧啶会导致酵母和肝细胞内卟啉的积累。
