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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ciofani, G. Lapenna, D. Bruno, C. Pierdomenico, S. D. Cuccurullo, F. |
| Description | Author Affiliation: Lapenna D ( Dipartimento di Medicina e Scienze dell'Invecchiamento, Università degli Studi G. d'Annunzio, Facoltà di Medicina e Chirurgia, 66100 Chieti, Italy.) |
| Abstract | Lipoprotein oxidation is crucial in atherogenic processes. Amiodarone is a lipophilic antiarrhythmic/antianginal drug which is able to influence the physicochemical status of biological lipid components. Since oxidation of lipids is affected by their physicochemical state and amiodarone binds to lipoproteins, we hypothesized that the drug may exert an antioxidant activity on human lipoprotein oxidation. Dose-dependent effects of therapeutically achievable amiodarone concentrations (1.5, 3, 5, 7 and 10 microM) were studied on copper-catalysed oxidation of the non-HDL fraction in vitro. Amiodarone inhibited oxidation as judged by generation of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH) and fluorescent products of lipoperoxidation (FPL) as well as from the kinetics of conjugated diene formation. This antioxidant activity was significant at 1.5 microM with total inhibition at 10 microM and an IC(50) of 4 microM. The primary in vivo metabolite of amiodarone, namely desethylamiodarone, also exhibited specific antioxidant properties although it was less effective than amiodarone with an IC(50) of 7 microM. In further in vivo experiments, susceptibility to copper-mediated oxidation of the non-HDL fraction was investigated before and 4 weeks after oral amiodarone administration to humans. Following treatment, significant inhibition of TBARS, LOOH and FPL generation was observed in comparison with baseline levels and a placebo-treated control group, highlighting an effective antioxidant capacity of amiodarone in vivo. Amiodarone did not change lipoprotein vitamin E and phospholipid content in vivo and did not show scavenging effects on oxidizing species involved in lipoprotein oxidation, such as peroxyl radicals, nor metal-binding/inactivating properties, suggesting that physicochemical modifications of lipoprotein lipids induced by the lipophilic drug may be involved in its antioxidant activity. In conclusion, amiodarone, and its primary metabolite desethylamiodarone, show previously unrecognized antioxidant activity on human lipoprotein oxidation. This effect is also evident in vivo and at therapeutically achievable drug concentrations. Thus, amiodarone may act as an antioxidant/antiatherosclerotic agent in humans, although this issue warrants further clinical study. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 133 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2001-07-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Amiodarone Pharmacology Antioxidants Lipoproteins Drug Effects Chemistry Anti-Arrhythmia Agents Copper Dose-Response Relationship, Drug Free Radical Scavengers Lipid Peroxidation Lipid Peroxides Metabolism Oxidation-Reduction Spectrometry, Fluorescence Thiobarbituric Acid Reactive Substances Time Factors Clinical Trial Controlled Clinical Trial |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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