[A new model for testing substances affecting the synthesis of heme].
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.
Kotal
P
P
Jirsa
M
M
Kaláb
M
M
Cervinka
J
J
Martásek
P
P
Kordac
V
V
D002738:Chloroquine / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006418:Heme / Q000096:biosynthesis; D011166:Porphyrins / Q000096:biosynthesis*; D011739:Pyrimethamine / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000378:metabolism
D011166:Porphyrins; D006418:Heme; D002738:Chloroquine; D011739:Pyrimethamine
Nový model pro testování látek ovlivnujících syntézu hemu.