[The property of tetracyclines to induce methemoglobin formation in erythrocytes and to inactivate catalase when exposed to radiation in the visible range].
When tetracycline and chlortetracycline were incubated an a dark room in the presence of erythrocytes with erythrocytic catalase completely inactivated by sodium azide, the antibiotics induced methemoglobin formation in them. If the catalase was not inactivated, no such phenomenon was observed. This meant that after the penetration into the erythrocytes the tetracyclines induced in them the generation of hydrogen peroxide which was the immediate cause of the methemoglobin formation. The effect of the methemoglobin formation on the erythrocytes was also induced by tetracycline without the catalase blocking when the erythrocytes were exposed to the antibiotic and visible light. The effect was not mediated by the hydrogen peroxide action on hemoglobin in the erythrocytes as it was in the previous case, since even when catalase was added exogenously to the suspension medium it induced no suppression of the methemoglobin formation in the erythrocytes. Additional introduction of exogenous catalase to the erythrocyte hemolysates prior to the exposure did not either influence the methemoglobin formation photoinduced in them by tetracycline. The effect manifestation was not practically influenced by L-histidine, mannitol or ethanol used as traps for the radicals which could form during the antibiotic exposure to visible light in the suspension medium. The calorimetric estimation of the catalase functional properties showed that when exposed to visible light in the presence of the enzyme (a commercial product) tetracycline induced its inactivation. It was indicated that the catalase photoinactivation by tetracycline was due not to a steady decrease of the activity of every molecule of the enzyme but to a dislodge of separate molecules among the active ones, i.e. a one-fold change of the enzyme molecule from the initial active state to the completely inactive one. The catalase photoinactivation by tetracycline was not eliminated by L-histidine or comparatively high concentrations of mannitol but was entirely eliminated by ethanol used in relatively low concentrations. When the erythrocytes were exposed to visible light in the presence of tetracycline, the effect of the catalase photoinactivation by the antibiotic was also observed. In this case the same as in the experiments with isolated catalase, ethanol as well protected the enzyme from the photoinactivation by tetracycline. The tetracycline photoeffects on hemoglobin, catalase and possibly other heme-containing proteins were likely realized in the immediate closeness of their hemes. The photoeffects of the tetracyclines associated with the heme-containing proteins possibly play a certain role in the phototoxicity of the antibiotics.
Petrenko
Iu M
IuM
Titov
V Iu
VIu
Vladimirov
Iu A
IuA
D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors* / Q000528:radiation effects; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D000431:Ethanol / Q000494:pharmacology; D005609:Free Radicals; D006639:Histidine / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008027:Light; D008353:Mannitol / Q000494:pharmacology; D008706:Methemoglobin / Q000096:biosynthesis*; D011817:Rabbits; D013754:Tetracyclines / Q000494:pharmacology*
D005609:Free Radicals; D013754:Tetracyclines; D000431:Ethanol; D008353:Mannitol; D006639:Histidine; D008706:Methemoglobin; D006861:Hydrogen Peroxide; D002374:Catalase