[Protection by blockers against human low density lipoprotein peroxidation induced by oxygen free radicals].
Previous studies in other systems have shown that beta-receptor blockers may effectively inhibit oxygen radical-induced lipid peroxidation. On the other hand, it has been recently proposed that oxygen free radicals can induce peroxidation of human low density lipoproteins (LDL), and that peroxidized LDL may be an atherogenic stimulus. Chemically modified LDL are internalized by macrophages via a specific cell surface receptor that was termed the scavenger receptor. This phenomenon may induce foam cells transformation in vivo. In the present study we investigated whether beta-blockers may reduce oxygen radical-mediated LDL peroxidation. Purified human LDL were oxidized by exposure to oxygen free radicals generated by xanthine (0.2 mM) and xanthine oxidase (100 mU) at 37 degrees C after a pre-incubation (30 min) in presence of different concentrations (from 1 to 30 microM) of acebutolol, metoprolol or propranolol, three agents with a different degree of lipophilicity. Peroxidation was measured from malonyldihaldehyde (MDA) production. Data have shown a significant percent inhibition of MDA formation in presence of beta-blockers (from 33 to 85%). Thus, beta-blockers reduced peroxidation of human LDL in vitro at clinically relevant concentrations. The order of potency appears to follow the degree of lipophilicity. These data suggest that, although beta-blockers are known to adversely effect lipid metabolism, these agents might on the other hand prevent atherogenesis via a mechanism of inhibition of LDL peroxidation in vivo and reduced foam cells formation.
Napoli
C
C
Cattedra di Cardiologia, Università di Napoli Federico II.
Ambrosio
G
G
Chiariello
P
P
Palumbo
G
G
Chiariello
M
M
D000070:Acebutolol / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D008790:Metoprolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D005609:Free Radicals; D008077:Lipoproteins, LDL; D008315:Malondialdehyde; D000070:Acebutolol; D011433:Propranolol; D008790:Metoprolol
Protezione da parte dei bloccanti della perossidazione delle lipoprotein umane a bassa densità indotta dai radicali liberi dell'ossigeno.