Inhibition of nonenzymatic protein glycation and lipid peroxidation by drugs with antioxidant activity.
We studied the effects of aminoguanidine (AG), beta-resorcylidene aminoguanidine (RAG), DL-penicillamine (PNCA) and captopril on early and advanced glycation of human serum albumin (HSA). We also assessed inhibition of lipid peroxidation by AG and RAG in erythrocytes. Incubation of HSA with D-glucose (20 mM, 37 degrees C for 21 days) led to the formation of Amadori products and fluorescent advanced glycation end-products (AGE). Only PNCA markedly reduced the formation of Amadori products, while all tested compounds markedly reduced the formation of AGE. AG and RAG also inhibited malondialdehyde formation in erythrocytes incubated with hydrogen peroxide. Addition of AG at concentrations from 1 microM to 1 mM caused a 10-80% inhibition of lipid peroxidation. Thus, AG and RAG inhibit toxic oxidative processes and may have therapeutic potential in a number of human diseases.
Jakus
V
V
Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
Hrnciarová
M
M
Cársky
J
J
Krahulec
B
B
Rietbrock
N
N
D000368:Aged; D000975:Antioxidants / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D003864:Depression, Chemical; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D016877:Oxidants / Q000494:pharmacology; D010396:Penicillamine / Q000494:pharmacology; D012709:Serum Albumin / Q000187:drug effects / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D006146:Guanidines; D016877:Oxidants; D012709:Serum Albumin; D017392:Thiobarbituric Acid Reactive Substances; C115168:resorcylidene aminoguanidine; D008315:Malondialdehyde; D002216:Captopril; D006861:Hydrogen Peroxide; D010396:Penicillamine; C004479:pimagedine