Influence of acetylsalicylic acid on oxidation of native and glycated low-density lipoprotein.
It is generally accepted that oxidation of low-density lipoproteins (LDL) is a causal factor in the development of atherosclerosis. Non-enzymatic glycosylation of LDL, i.e."glycation", plays a central role in late complications of diabetes mellitus and may initiate and/or accelerate the oxidation process. Therefore, the inhibition of this processes is of major therapeutic relevance. The influence of acetylsalicylic acid (ASA) on the oxidation of native and glycated LDL was studied in vitro. LDL (0.25 mg protein/ml ) was oxidatively modified with 5.0 microM CuSO4. Only at "supratherapeutical" ASA concentrations in the range 0.06-2.0 mg /ml we found a significant concentration-dependent inhibition of LDL oxidation both for native and glycated LDL, which was from 0.2 mg/ml upwards significantly more marked for native LDL than for glycated LDL. The maximal inhibitory effect occurred at 2.0 mg/ml with 89.6% inhibition of LDL-oxidation for native LDL and 64.4% for glycated LDL. At 0.2 mg/ml ASA the respective inhibitory values were 38.5% and 31.0%. For glycated LDL the ASA doses of maximal- and approximately 50%-inhibition, as found for native LDL, were chosen to investigate the inhibitory effect on 2,4,8 and 24 hours oxidation of glycated LDL to monitor the time-dependency of inhibition by ASA. This revealed that ASA only delayed, not permanently inhibited LDL oxidation.
Sobal
G
G
Department of Nuclear Medicine, University of Vienna, Austria.
Menzel
J E
JE
Sinzinger
H
H
D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D017127:Glycation End Products, Advanced; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D000093844:Glycated Proteins
D001241:Aspirin; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins