Aminoguanidine inhibits the modification of proteins by lipid peroxidation derived aldehydes: a possible antiatherogenic agent.
The reaction of protein amino groups with lipid-peroxidation-derived aldehydes (LPDA) has been shown to play a key role in various pathological processes. Especially important is the reaction of LPDA with apolipoprotein B during oxidative modification of low density lipoprotein (LDL), which leads to its enhanced uptake by macrophages and, eventually, to atherogenesis. Since aminoguanidine, a drug which inhibits the advanced steps of glycation (probably by trapping reactive sugar-derived aldehydes), has been proposed as a therapeutic agent for the prevention of late diabetic complications, we have tested its ability to interfere with the modification of proteins by LPDA. LDL was incubated with cupric ions. Aminoguanidine at 5, 10 and 25 mM inhibited both the increase in electrophoretic mobility of LDL and the generation of thiobarbituric acid reactive substances (TBARS) (P < 0.001). It also inhibited the increase in electrophoretic mobility and 260-400 nm absorbance of bovine serum albumin incubated with malondialdehyde. These results suggest that aminoguanidine may have an antiatherogenic effect.
Laboratorio Central, Hospital General de Galicia, Santiago, Spain.
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Requena
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Vidal
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Cabezas-Cerrato
D000447:Aldehydes; D001055:Apolipoproteins B / Q000737:chemistry* / Q000378:metabolism; D001161:Arteriosclerosis / Q000503:physiopathology / Q000517:prevention & control*; D004587:Electrophoresis, Agar Gel; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000187:drug effects; D013053:Spectrophotometry; D017392:Thiobarbituric Acid Reactive Substances
D000447:Aldehydes; D001055:Apolipoproteins B; D006146:Guanidines; D008077:Lipoproteins, LDL; D011506:Proteins; D017392:Thiobarbituric Acid Reactive Substances; D012710:Serum Albumin, Bovine; C004479:pimagedine