Effects of Hydrazyl Group Containing Drugs on Leucocyte Functions: An Immunoregulatory Model for the Hydralazine-Induced Lupus-Like Syndrome

Autor: Schopf, Rudolf, Hanauske-Abel, Hartmut, Tschank, Georg, Schulte-Wissermann, Hermann, Günzler, Volkmar
Zdroj: Immunopharmacology and Immunotoxicology; 1985, Vol. 7 Issue: 4 p385-401, 17p
Abstrakt: Isoniazid (INH) and hydralazine (HYD) are transglutaminase (T Gase, E. G. 2.3.2.13.) substrates containing catalytically recruit-able hydrazyl groups. Since they can be expected to inhibit TGase-mediated cell functions by competing with physiological substrates, their effect upon allogeneically and lectin-induced proliferation of mononucleocytes and upon zymosan-induced chemiluminescence of phagocytes was studied.Both compounds inhibited chemiluminescence in a dose-dependent manner. ID50 of HYD was consistently below 20 uM, while that of INH was above 120 μM. Proliferation of immunocompetent cells was suppressed by HYD with an ID50 of 60 μM, INH was inhibitory only above 5000 μM. Analogs of both compounds not containing hydrazyl groups proved to be inactive. Control experiments indicated that inhibition is not due to toxicity or lipophilicity of the compounds, structural analogs lacking a hydrazyl moiety were inactive.
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