Protective effects of beta-blockers against 2,2'-azobis(2-amidinopropane)-dihydrochloride-induced damage.
The protective effects of beta-blockers against 2,2'-azobis(2- amidinopropane)-dihydrochloride (AAPH)-induced damage were investigated. With the exception of pindolol, none of the beta-blockers tested inhibited arachidonate peroxidation induced by AAPH in the absence of iron. In contrast, ADP-Fe(3+)- and NADPH-dependent microsomal lipid peroxidation was inhibited by all the beta-blockers tested, although the inhibitory effects of atenolol and metoprolol were very slight. Oxidation of tryptophan residues in bovine serum albumin (BSA) induced by AAPH was strongly inhibited by pindolol and propranolol but not by atenolol or metoprolol. All the beta-blockers tested, however, inhibited AAPH-induced carbonyl formation of BSA. Furthermore, all the beta-blockers tested also strongly inhibited the deoxyribose degradation induced by AAPH, suggesting that these agents act as hydroxyl radical scavengers to inhibit carbonyl formation. DNA strand scission was induced by AAPH in the absence or presence of O2. Only pindolol strongly inhibited the DNA damage in the absence of O2. In the presence of O2, however, all the beta-blockers tested effectively prevented the DNA damage. These results suggested that the hydroxyl radicals produced from AAPH damaged DNA and, that beta-blockers might act as hydroxyl radical scavengers to protect DNA against the AAPH-induced oxidative damage.
Miura
T
T
Hokkaido Institute of Pharmaceutical Sciences, Otaru, Japan.
Muraoka
S
S
Ogiso
T
T
D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000494:pharmacology*; D000578:Amidines / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry; D004249:DNA Damage; D005609:Free Radicals; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000737:chemistry; D008862:Microsomes, Liver / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D051381:Rats
D000319:Adrenergic beta-Antagonists; D000578:Amidines; D005609:Free Radicals; D008054:Lipid Peroxides; D011506:Proteins; D016718:Arachidonic Acid; C046728:2,2'-azobis(2-amidinopropane)