The peroxidation step in lipid transformation is considered to be essential in 
the pathogenesis of atherosclerosis. Calcium antagonists (CA) appear to have 
antioxidant effects in addition to their potent vasorelaxant properties. In the 
present study, we compared the antioxidative efficacy of CA (amlodipine, 
lacidipine, nifedipine, isradipine, diltiazem, and semotiadil) in the 
copper-catalysed oxidation of low-density lipoprotein (LDL) with that of 
glycated(g)/glycoxidated(go) LDL. This issue is of great importance when 
considering the potential therapeutic use of antioxidant drugs in 
diabetes-associated vasculopathy. Oxidation of native LDL was inhibited most 
efficiently (>90%) by lacidipine and semotiadil in the concentration range 
10(-4)-10(-3) M. We found, however, a dramatic decrease in antioxidant activity 
towards g/goLDL as compared to native LDL in all the CA tested. Only lacidipine 
significantly inhibited copper-mediated oxidation of g/goLDL in the whole 
concentration range tested (10(-5) M-10(-3) M). This probably resulted from the 
increased auto-oxidative potential introduced by early and advanced glycation 
end products (AGE) into the g/goLDL. We noted that coincubation of LDL with 
10(-3) M CA and 0.5 M glucose under oxidative/non-oxidative conditions partially 
or fully restored the antioxidant capacity of the different CA to inhibit the 
subsequent copper-catalysed oxidation of the modified LDL. This is a clear 
indication that CA inhibit glycative or glycoxidative LDL changes during the 
preceding long-term glycation period. The notion that both oxidative changes and 
long-term glycation effects were reduced by CA was corroborated by fluorescence 
analysis, AGE-ELISA, quantitation of lipid peroxidation, and thiobarbituric acid 
reactive substance (TBARS) measurement of long-term g/goLDL. The strongest 
antioxidative effects during long-term glycation of LDL were seen with 
isradipine, lacidipine, nifedipine, and semotiadil. Diltiazem was the only CA 
that could not prevent TBARS formation in LDL during the long-term glycation 
period. In contrast, Amadori product formation, as measured by the generation of 
fructosamines, was not significantly reduced by any CA tested. Thus CA, like 
other antioxidants, significantly retard AGE formation, while initial glycation 
reactions, such as Amadori product formation, are only weakly inhibited.