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Updated: Jul 14, 2026
07:29
Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
Amiodarone inhibits tocopherol-mediated human lipoprotein peroxidation
Domenico Lapenna1, Giuliano Ciofani, Sante Donato Pierdomenico
1Dipartimento di Medicina e Scienze dell'Invecchiamento and Centro di Scienze dell'Invecchiamento-Fondazione Università G. d'Annunzio, Facoltà di Medicina e Chirurgia, Chieti, Italy. piersd@tiscalinet.it
Biochemical Pharmacology
|May 29, 2007
Summary
Drug basicity and hydrophobicity influence lipoprotein tocopherol-mediated peroxidation (TMP). Amiodarone, a hydrophobic drug, inhibits TMP at therapeutic levels, suggesting potential clinical relevance for antioxidant strategies.
Area of Science:
- Biochemistry
- Pharmacology
- Lipid Metabolism
Background:
- Lipoprotein tocopherol-mediated peroxidation (TMP) is a key process in oxidative stress.
- The influence of drug physicochemical properties on TMP is not well understood.
Purpose of the Study:
- To investigate the effect of amiodarone, an extremely hydrophobic drug, on human non-high-density lipoprotein (non-HDL) TMP.
- To determine the role of drug basicity and hydrophobicity in TMP inhibition.
Main Methods:
- Studied the inhibition of TMP by amiodarone and other hydrophobic compounds in human lipoproteins.
- Assessed the correlation between drug hydrophobicity, basicity, and anti-TMP potency.
- Investigated the effect of alpha-tocopherol enrichment on amiodarone's efficacy.
Main Results:
- Amiodarone significantly inhibited TMP at therapeutic concentrations (IC50 = 5microM), comparable to ascorbic acid.
- Inhibition potency of hydrophobic cationic amphiphiles correlated with their hydrophobicity.
- Drug basicity was identified as a critical factor for TMP inhibition, while acidic or neutral compounds were ineffective.
- Amiodarone's effectiveness decreased with lipoprotein alpha-tocopherol enrichment.
Conclusions:
- Drug basicity and hydrophobicity are the primary determinants of TMP inhibition.
- Amiodarone exhibits anti-TMP properties at therapeutic concentrations, potentially relevant in clinical settings.
- The mechanism involves interactions with lipoprotein alpha-tocopherol and lipids, reducing radical transfer and peroxidation.
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