Abstract

The structural integrity, elasticity, and fluidity of lipid membranes are critical for cellular activities such as communication between cells, exocytosis, and endocytosis. Unsaturated lipids, the main components of biological membranes, are particularly susceptible to the oxidative attack of reactive oxygen species. The peroxidation of unsaturated lipids, in our case 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), induces the structural reorganization of the membrane. We have employed a multi-technique approach to analyze typical properties of lipid bilayers, i.e., roughness, thickness, elasticity, and fluidity. We compared the alteration of the membrane properties upon initiated lipid peroxidation and examined the ability of flavonols, namely quercetin (QUE), myricetin (MCE), and myricitrin (MCI) at different molar fractions, to inhibit this change. Using Mass Spectrometry (MS) and Fourier Transform Infrared Spectroscopy (FTIR), we identified various carbonyl products and examined the extent of the reaction. From Atomic Force Microscopy (AFM), Force Spectroscopy (FS), Small Angle X-Ray Scattering (SAXS), and Electron Paramagnetic Resonance (EPR) experiments, we concluded that the membranes with inserted flavonols exhibit resistance against the structural changes induced by the oxidative attack, which is a finding with multiple biological implications. Our approach reveals the interplay between the flavonol molecular structure and the crucial membrane properties under oxidative attack and provides insight into the pathophysiology of cellular oxidative injury.

Highlights

  • Lipid peroxidation is a complex process associated with the oxidative deterioration of lipids and the production of various breakdown products [1,2]

  • Most studies of the antioxidant activity of different flavonols have been performed in oils [50], emulsions [51,52,53], and low density lipoproteins (LDL) [54,55,56]

  • The antioxidant activity of MCE has been shown to be more effective than QUE in oils in a study of oxidative processes by chelating metal ions [57], while the opposite effect has been found in fish phospholipid liposomes by measuring the amount of thiobarbituric acid-reactive substances (TBARS) produced [58]

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Summary

Introduction

Lipid peroxidation is a complex process associated with the oxidative deterioration of lipids and the production of various breakdown products [1,2]. Lipid peroxidation occurrence in the human body is a consequence of oxidative stress, which has been correlated with various diseases and health conditions, including neurodegenerative diseases, heart and cardiovascular system conditions, inflammatory immune injuries, and others [4]. It has been suggested that some peroxidation products, in particular malondialdehyde (MDA), 4-hydroxy-2,3-nonenal (HNE), and other 4-hydroxy-2,3-alkenals (HAKs) of different chain lengths can affect several cell functions, including signal transduction, gene expression, cell proliferation, and the response of the target cell [5]. Cajone and Bernelli-Zazzera [6] showed that HNE caused an increase in the expression of the hsp 70 gene in human hepatoma cells.

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