Summary
Incubation with MNS at a concentration of 2×10−5 M inhibits 51.7±15.6% of the GSH-px activity in hemolysates, while concentrations ranging between 5×10−5 and 1×10−4 M lead to 100% inhibition. 1×10−4 M MNS in hemoglobin free enzyme solution results in 70% inhibition. The incubation of hemolysates and Hb free GSH-px solution with menadione in concentrations ranging between 2 and 4×10−4 M results in 44 to 70% inhibition. The inhibition appears to be of the non-competitive type and not to be reversed by dialysis. Though MNP at a concentration of 2×10−2 M does not inhibit GSH-px both in hemolysates and Hb-free GSH-px preparations. Na2S2O5 at concentrations of 1×10−3 M produces 50% inhibition of GSH-px. The accumulation of H2O2 caused by the presence of the autoxidable menadione and MNS and by the inhibition of GSH-px might impair the GSH-mediated protective mechanism against oxidative damage in the erythrocytes. Consequently, further oxidation of hemoglobin and of SH groups of the red cell membrane could lead to hemolysis.
Zusammenfassung
Die Inkubation mit MNS in einer Konzentration von 2×10−5 M hemmt die GSH-px-Aktivität in Hämolysaten zu 51,7% (±15,6%), während Konzentrationen von 5×10−5 und 1×10−4 M zu einer vollständigen Hemmung führen. Hämoglobinfreie Enzymlösungen werden durch 1×10−4 M MNS nur zu 70% gehemmt.
Inkubationen von Hämolysaten und Hb-freien GSH-px-Lösungen mit Menadion von 2 bzw. 4×10−4 M führt zu 44%iger bzw. 70%iger Hemmung. Diese Hemmung scheint nicht kompetitiv zu sein und ist durch eine Dialyse nicht reversibel.
MNP hemmt dagegen selbst bei 2×10−2 M die GSH-px weder in Hämolysaten noch in Hb-freien Präparationen.
Na2S2O5 ergibt bei 1×10−3 M eine 50%ige Hemmung der GSH-px.
Die Akkumulation von H2O2, die sowohl durch das autoxidable Menadion und MNS als auch durch eine Hemmung der GSH-px hervorgerufen sein kann, könnte den durch GSH bewirkten Schutz vor oxidativer Schädigung in den Erythrocyten verschlechtern. Somit kann eine Oxidation des Hämoglobins und der SH-Gruppen in der Zellmembran zur Hämolyse führen.
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Vetrella, M., Barthelmai, W. Studies on drug-induced hemolysis: Effects of menadione and its water soluble preparations on the glutathione peroxidase of human erythrocytes. Klin Wochenschr 50, 234–238 (1972). https://doi.org/10.1007/BF01486527
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DOI: https://doi.org/10.1007/BF01486527