phores, AGE epitopes, and oxidized lipids appeared to follow
similar, nonlinear reaction kinetics (Fig. 3).
Aminoguanidine prevents AGE formation by reacting with
glucose-derived products that form at intermediate stages of
the advanced glycosylation pathway. Early Amadori products,
for example, rearrange to dideoxyosones that react with
aminoguanidine to form triazine or dihydrazone products
(30). Thus, aminoguanidine also might react directly with the
aldehydes that form during fatty acid oxidation. In agreement
with recent reports (31, 32), the addition of aminoguanidine
to MDA inhibited the formation of TBA-reactive substances
in a concentration-dependent manner (data not shown).
These data suggest that aminoguanidine inhibits AGEmediated
fatty acid oxidation by two mechanisms: inhibition
of lipid advanced glycosylation and by direct reaction with
reactive aldehydes that form during fatty acid oxidation.
The contribution of advanced glycosylation to the oxidative
modification of LDL first was assessed by incubating
LDL with glucose in vitro in the presence of EDTA. LDL was