Prooxidant action of carazolol in the Fenton-like reaction

Carazolol [4-(2-hydroxy-3-isopropyl-amino-propoxy)-carbazole], a β(3)-adrenoceptor agonist, is clinically used in the treatment of hypertension, cardiac arrhythmias and angina pectoris. Despite the beneficial effect of the drug, its high dose may contribute to cardiotoxicity. This study was conducted to examine whether carazolol can influence hydroxyl radical formation by a Fenton-like reaction [Co(II) + H(2)O(2) + HO(-)] in the presence of ethylenediaminetetraacetic acid. The oxygen free radicals and singlet oxygen ((1)O(2)) formation was traced by three different assay methods: chemiluminescence (CL), an electron spin resonance (ESR) spin trapping with 2,2,6,6-tetramethyl-4-piperidine and 5,5-dimethyl-1-pyrroline-1-oxide, and spectrophotometric determination of (1)O(2) based on bleaching of p-nitrosodimethylaniline. The effect of hydroxyl radical inhibitors and (1)O(2) quenchers on peroxidation of carazolol was also examined. The results indicated that carazolol enhanced the HO radical and (1)O(2) formation in a Fenton-like reaction.