Protection of low density lipoprotein oxidation at chemical and cellular level by the antioxidant drug dipyridamole

L. Iuliano, A. R. Colavita, C. Camastra, V. Bello, C. Quintarelli, M. Alessandroni, F. Piovella, F. Violi

Research output: Contribution to journalArticle

Abstract

1. The oxidative modification of low density lipoprotein (LDL) is thought to be an important factor in the initiation and development of atherosclerosis. Natural and synthetic antioxidants have been shown to protect LDL from oxidation and to inhibit atherosclerosis development in animals. Synthetic antioxidants are currently being tested, by they are not necessarily safe for human use. 2. We have previously reported that dipyridamole, currently used in clinical practice, is a potent scavenger of free radicals. Thus, we tested whether dipyridamole could affect LDL oxidation at chemical and cellular level. 3. Chemically induced LDL oxidation was made by Cu(II), Cu(II) plus hydrogen peroxide or peroxyl radicals generated by thermolysis of 2,2'-azo-bis(2-amidino propane). Dipyridamole, (1-10 μM), inhibited LDL oxidation as monitored by diene formation, evolution of hydroperoxides and thiobarbituric acid reactive substances, apoprotein modification and by the fluorescence of cis-parinaric acid. 4. The physiological relevance of the antioxidant activity was validated by experiments at the cellular level where dipyridamole inhibited endothelial cell-mediated LDL oxidation, their degradation by monocytes, and cytotoxicity. 5. In comparison with ascorbic acid, α-tocopherol and probucol, dipyridamole was the more efficient antioxidant with the following order of activity: dipyridamole > probucol > ascorbic acid > α-tocopherol. The present study shows that dipyridamole inhibits oxidation of LDL at pharmacologically relevant concentrations. The inhibition of LDL oxidation is unequivocally confirmed by use of three different methods of chemical oxidation, by several methods of oxidation monitoring, and the pharmacological relevance is demonstrated by the superiority of dipyridamole over the naturally occurring antioxidants, ascorbic acid and α-tocopherol and the synthetic antioxidant probucol.

Original languageEnglish
Pages (from-to)1438-1446
Number of pages9
JournalBritish Journal of Pharmacology
Volume119
Issue number7
Publication statusPublished - 1996

Keywords

  • Antioxidants
  • Atherosclerosis
  • Dipyridamole
  • Free radicals
  • Lipoproteins

ASJC Scopus subject areas

  • Pharmacology

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    Iuliano, L., Colavita, A. R., Camastra, C., Bello, V., Quintarelli, C., Alessandroni, M., Piovella, F., & Violi, F. (1996). Protection of low density lipoprotein oxidation at chemical and cellular level by the antioxidant drug dipyridamole. British Journal of Pharmacology, 119(7), 1438-1446.