M. Gamberini et Lcc. Leite, CARBON-CENTERED FREE-RADICAL FORMATION DURING THE METABOLISM OF HYDRAZINE DERIVATIVES BY NEUTROPHILS, Biochemical pharmacology, 45(9), 1993, pp. 1913-1919
The neutrophil-catalyzed metabolism of hydrazine derivatives to carbon
-centered radicals was investigated by the spin-trapping technique usi
ng alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN). Oxidation of
methylhydrazine (MeH), dimethylhydrazine (DMH), phenylethylhydrazine o
r procarbazine by neutrophils from rat peritoneal exudates led to the
formation of alkyl radicals. The monosubstituted hydrazine oxidation b
y phorbol ester (PMA)- or Zymocel-activated neutrophils generated, on
average, 2- to 4-fold more POBN-alkyl adducts than di-substituted hydr
azines. Supernatant from sonicated neutrophils generated similar yield
s of radicals. Azide, an inhibitor of myeloperoxidase, effectively red
uced the neutrophil-catalyzed radical yield from the oxidation of MeH
but not DMH. On the other hand, superoxide dismutase and catalase effe
ctively inhibited radical formation in DMH metabolism by PMA-activated
neutrophils, in contrast to MeH metabolism. Our results show that neu
trophils are able to metabolize hydrazine derivatives, the pathway dep
ending on the hydrazine substitution. Alkyl radical production during
the oxidation of mono-substituted derivatives, such as MeH, was mediat
ed mainly by myeloperoxidase, and that of di-substituted derivatives,
such as DMH, was mediated mainly by active oxygen species.