A potent antioxidant, SB209995, inhibits oxygen-radical-mediated lipid peroxidation and cytotoxicity.
The antioxidant activity of SB209995, a metabolite of carvedilol in human, was studied and compared with its parent compound, carvedilol. SB209995 or carvedilol inhibited iron-catalyzed lipid peroxidation assessed as thiobarbituric acid-reactive substance generated in brain homogenate with IC50s of 0.30 and 8.1 mumol/l, respectively. The oxidation of low-density lipoprotein (LDL) by macrophages or that initiated by Cu2+ ions was inhibited by SB209995 with IC50s of 59 nmol/l and 1.7 mumol/l, respectively. Under the same conditions, the IC50s of carvedilol were 3.8 and 17.1 mumol/l, respectively. Furthermore, SB209995 protected cultured endothelial cells against hydroxyl radical (OH.) or superoxide (O2-)-mediated lipid peroxidation and cytotoxicity, assessed as lactate dehydrogenase release and cell death. The results indicate that SB209995 is a more potent antioxidant than carvedilol and may contribute to the therapeutic effects of carvedilol.
Feuerstein
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R
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa. 19406-0939.
Yue
T L
TL
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects; D005609:Free Radicals; D006801:Humans; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism; D010100:Oxygen; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D013481:Superoxides / Q000037:antagonists & inhibitors; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D000975:Antioxidants; D002227:Carbazoles; D005609:Free Radicals; D008077:Lipoproteins, LDL; D011412:Propanolamines; D000077261:Carvedilol; D013481:Superoxides; C088570:SB 209995; D017665:Hydroxyl Radical; D014969:Xanthine Oxidase; D010100:Oxygen