[Inhibition of porphyrin synthesis by isonicotinic acid hydrazide in models simulating porphyria].
Increased activity of haem synthesis key enzyme is a common phenomenon in hepatic porphyrias. Synthase activity of delta-aminolevulinic acid is extensively increased in acute hepatic porphyrias or it can be by means of feedback moderately secondarily increased in their chronic forms. Isonicotinic acid hydrazide (INH) is a competitive inhibitor of delta-aminolevulinic acid synthase as it combines with enzyme co-factor, pyridoxalphosphate (PDX) to form hydrazone. The INH porphyrinstatic effects were verified by testing two experimental models. The yeast model exhibited 5-fold inhibition at 10 mM INH concentration in medium. The chicken germ model after a 10 microM INH dose exhibited 82% inhibition. This inhibition can be eliminated by PDX administration to reach the original porphyrin synthesis at equimolar INH and PDX concentrations. Histological study of transversal chicken liver sections proved that 1 microM INH administration does not result in disturbance of chicken hepatocyte integration. The suggested preparation has the advantage of being commonly manufactured and approved to be used in human medicine.
Kotal
P
P
Klepácek
I
I
Jirsa
M
M
Kordac
V
V
D000818:Animals; D002642:Chick Embryo; D007538:Isoniazid / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D011164:Porphyrias / Q000378:metabolism; D011166:Porphyrins / Q000096:biosynthesis*; D011732:Pyridoxal Phosphate / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
D011166:Porphyrins; D011732:Pyridoxal Phosphate; D014508:Urea; C005700:apronalide; D007538:Isoniazid
Inhibice syntézy porfyrinu hydrazidem kyseliny isonikotinové na modelech simulujících porfyrii.