Cholesterol-nitrone conjugates as protective agents against lipid oxidation: A model membrane study

Abstract

Free radical scavengers such as α-phenyl-N-tert-butylnitrone (PBN) have been widely used as protective agents in several biological models. We recently designed two PBN derivatives by adding a cholesterol moiety to the parent nitrone to increase its lipophilicity. In addition to the cholesterol, a sugar group was also grafted to enhance the hydrophilic properties at the same time. In the present work we report on the synthesis of a third derivative bearing only a cholesterol moiety and the physical chemical and antioxidant characterization of these three derivatives. We demonstrated they were able to form stable monolayers at the air/water interface and with the two derivatives bearing a sugar group, repulsive interactions with 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) were observed. We next investigated the interaction with DLPC on a liposome model. Fluorescence spectroscopy experiments showed the addition of a cholesterol moiety causes an ordering effect whereas the presence of the sugar group led to a disordering effect. The protective effect against lipid oxidation was then investigated using dynamic light scattering and the formation of conjugated dienes was quantified spectrophotometrically. Two oxidizing systems were tested, i.e. the AAPH-thermolysis which generates peroxyl radicals and the Fenton reagent which is responsible of the formation of hydroxyl radicals. Due to their membrane localization, the three cholesteryl-PBN derivatives are able to prevent lipid oxidation with the two types of radical inducers but with a different mode of action.

The Interaction of Gb3 Glycosphingolipids with ld and lo Phase Lipids in Lipid Monolayers Is a Function of Their Fatty Acids

“…High log P values indicate a strong membrane partitioning and pronounced lipophilic properties . All synthetic Gb 3 glycosphingolipids have large log P values, even larger (in the case of C 24 fatty acids) than those of DOPC, SM 18 , and cholesterol, which are known to form stable monolayers at the air–water interface. − Thus, we expected that the Gb 3 glycosphingolipids also generate stable monolayers, similar to the one recorded by Watkins et al using a mixture of Gb 3 lipids extracted from red blood cells.…”

Recent Advances on Nitrones Design for Stroke Treatment

“…The new conjugates are PBN-ChN hybrids, where the central PBN core has been decorated with the lipophilic cholesterol and hydrophilic sugar-like motifs at the head and tail of the novel conjugate, using diverse strategic designs . This analysis resulted in the synthesis of ChNs chol-PBN ( 20 ), L-PBN-chol ( 21 ), or chol-PBN-L ( 22 ) (Figure ). In particular, nitrones 21 and 22 exhibited potent capacity to protect 1,2-dilinoleoyl- sn -glycero-3-phosphocholine liposomes from oxidation, whereas nitrone 22 (Figure ) but not 21 remarkably protected the retina against bright fluorescent light exposition when injected into the vitreous at 1 mM, overcoming the standard nitrone 3 (Figure ), as it showed protective power at 9 mM but not at 1 mM.…”

“…This analysis resulted in the synthesis of ChNs chol-PBN ( 20 ), L-PBN-chol ( 21 ), or chol-PBN-L ( 22 ) (Figure ). In particular, nitrones 21 and 22 exhibited potent capacity to protect 1,2-dilinoleoyl- sn -glycero-3-phosphocholine liposomes from oxidation, whereas nitrone 22 (Figure ) but not 21 remarkably protected the retina against bright fluorescent light exposition when injected into the vitreous at 1 mM, overcoming the standard nitrone 3 (Figure ), as it showed protective power at 9 mM but not at 1 mM. Accordingly, nitrone 22 might be considered as a hit agent for the therapy of retina pathologies …”

Quality Evaluation of Drinks Based on Liposome Shape Changes Induced by Flavor Molecules

“…Previous studies have analyzed the interaction between liposomes and biomolecules such as capsaicin, oxidized cholesterol, − local anesthetics, , proteins, and polyphenols, . Moreover, dynamic shape changes are induced by several stimulations such as differences in protein aggregation level, , different polyphenol structures, strength of stimulation on the surfactant, and photo-oxidation of lipids. ,, …”