Doxazosin treatment and peroxidation of low-density lipoprotein among male hypertensive subjects: in vitro and ex vivo studies
| Autor: | K Valnes, Marit S. Nenseter, Christian A. Drevon, Jon E Arnstad, Ingeborg R. Brude, Kjersti Viken |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Male medicine.medical_specialty Antioxidant medicine.medical_treatment Bepridil Amidines medicine.disease_cause Biochemistry Antioxidants Lipid peroxidation chemistry.chemical_compound Picrates Internal medicine medicine Doxazosin Humans Antihypertensive Agents Aged Pharmacology Biphenyl Compounds Free Radical Scavengers Middle Aged Oxidants Lipoproteins LDL Endocrinology chemistry Low-density lipoprotein Hypertension Lipid Peroxidation Copper Ex vivo Oxidative stress Drug metabolism medicine.drug Lipoprotein |
| Zdroj: | Biochemical Pharmacology. 58:183-191 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/s0006-2952(99)00057-x |
| Popis: | Doxazosin is an antihypertensive drug that gives rise to 6- and 7-hydroxydoxazosin during hepatic metabolism. The structures of the hydroxymetabolites suggest that they may possess antioxidative properties. The aim of the present study was to examine whether doxazosin and 6- and 7-hydroxydoxazosin were able to scavenge free radicals and whether these compounds might protect low-density lipoprotein (LDL) against in vitro and ex vivo oxidation. Both 6- and 7-hydroxydoxazosin showed radical scavenging capacity as assessed by measuring scavenging of 1,1-diphenyl-2-picrylhydrazyl radicals. In vitro incubation with 10 μM 6- and 7-hydroxydoxazosin significantly reduced human mononuclear cell-mediated oxidation of LDL, measured as the formation of lipid peroxides and the relative electrophoretic mobility of LDL (to 10 and 6% of the control, respectively). Furthermore, formation of conjugated dienes in LDL during Cu2+-induced oxidation was significantly reduced in the presence of 5 μM 6- and 7-hydroxydoxazosin (to 28% of tmax [time to maximum] of control). However, treatment of hypertensive patients with increasing doses of doxazosin (from 1 to 8 mg/day) for 8 weeks altered neither Cu2+-catalyzed, 2,2′azobis-(2-amidinopropane hydrochloride)-initiated, nor cell-mediated oxidation of patient LDL ex vivo. Furthermore, the total antioxidative capacity of plasma was unaffected by treatment. In conclusion, the present study shows that 6- and 7-hydroxydoxazosin have radical scavenging properties and protect LDL against in vitro oxidation. However, treatment of hypertensive male subjects with increasing doses of doxazosin for 8 weeks did not affect ex vivo oxidation of LDL. |
| Databáze: | OpenAIRE |
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