Daniel Jore
University of Paris
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Featured researches published by Daniel Jore.
Journal of Pineal Research | 2005
J. Mekhloufi; D. Bonnefont‐Rousselot; Said Yous; Daniel Lesieur; Martine Couturier; Patrice Therond; A. Legrand; Daniel Jore; Monique Gardès-Albert
Abstract: This study aimed at investigating the in vitro protective effects of GWC22, a novel pinoline derivative [6‐ethyl‐1‐(3‐methoxyphenyl)‐2‐propyl‐1,2,3,4‐tetrahydro‐beta‐carboline] chlorhydrate, against radiation‐induced oxidation of linoleate initiated by hydroxyl radicals (•OH). Using linoleate micelles (10−2 m) as lipid model, two indexes of peroxidation have been measured, i.e. conjugated dienes and hydroperoxides. Similar determinations were performed with melatonin in order to compare the protective effects of the two compounds. It was observed that, the higher the concentration of GWC22 (or melatonin) (3 × 10−5 to 10−4 m), the stronger the antioxidant ability. In these in vitro assays, GWC22 showed a better antioxidant effect than melatonin for a given antioxidant concentration. A reaction scheme has been proposed to explain the inhibitory effect of an antioxidant via the propagating steps of the lipid peroxidation. Indeed, we have suggested that melatonin and GWC22 may compete with the fatty acid to scavenge lipid peroxyl radicals (LOO•). We have estimated a lower limit for the LOO• rate constant for GWC22 (≥1.4 × 105/m/s) and for melatonin (≥2.8 × 104/m/s) assuming that the k‐value of the propagating step in linoleate (LOO• + linoleate) was 1.4 × 103/m/s. The difference of reactivity between melatonin and GWC22 in this model system is assumed to be related to their relative lipophilicity.
Journal of Pineal Research | 2002
Dominique Bonnefont-Rousselot; Gwénaël Chevé; Andrea Gozzo; Anne Tailleux; Virginie Guilloz; Stéphanie Caisey; Elisabeth Teissier; Jean-Charles Fruchart; Jacques Delattre; Daniel Jore; Daniel Lesieur; Patrick Duriez; Monique Gardès-Albert
Abstract: This study was designed to evaluate the protective effect of two melatonin related compounds towards low density lipoproteins (LDL) oxidation initiated in vitro either by defined free radicals [i.e. superoxide anion (O2·–) and ethanol‐derived peroxyl radicals (RO2·)] produced by gamma radiolysis or by copper ions. The compounds studied were N‐[2‐(5‐methoxy‐1H‐indol‐3‐yl)ethyl]‐3,5‐di‐tert‐butyl‐4‐hydroxybenzamide (DTBHB) and (R,S)‐1‐(3‐methoxyphenyl)‐2‐propyl‐1,2,3,4‐tetrahydro‐β‐carboline (GWC20) which is a pinoline derivative. Their effects were compared with those of melatonin at the same concentration (100 μmol/L). None of the three tested compounds protected endogenous LDL α‐tocopherol from oxidation by RO2·/O2·– free radicals. By contrast, they all protected β‐carotene from the attack of these free radicals with GWC20 being the strongest protector. Moreover, melatonin and DTBHB partially inhibited the formation of products derived from lipid peroxidation (conjugated dienes and thiobarbituric acid‐reactive substances or TBARS) while GWC20 totally abolished this production. As previously shown, melatonin (at the concentration used) inhibited copper‐induced LDL oxidation by increasing 1.60‐fold the lag phase duration of conjugated diene formation over the 8 hr of the experimental procedure, however, DTBHB and GWC20 were much more effective, because they totally prevented the initiation of the propagation phase of LDL oxidation. It would be interesting to test in vivo if DTBHB and GWC20 which exhibit a strong capacity to inhibit in vitro LDL oxidation would reduce or not atherosclerosis in animals susceptible to this pathology.
Radiation Research | 1997
Dominique Bonnefont-Rousselot; Abdelouahed Khalil; Jacques Delattre; Daniel Jore; Monique Gardès-Albert
The aim of this work was to specify the mechanisms involved in the radical oxidation of human high-density lipoprotein (HDL) and to compare these mechanisms with those described previously for the oxidation of low-density lipoprotein (LDL) under the same experimental conditions (Bonnefont-Rousselot et al., Radiat, Res. 134, 271-282, 1993). The oxidation of HDL, initiated by .OH or .OH/O(.-)2 free radicals from gamma radiolysis of water, was evaluated as a function of increasing radiation dose by analyzing quantitatively the decrease of endogenous alpha-tocopherol and the formation of oxidation products (thiobarbituric acid-reactive substances and conjugated dienes). All qualitative conclusions were supported by quantitative data (radiation yields and concentrations of the oxidation markers at high radiation doses) and by the mechanisms of the kinetics, .OH free radicals in the absence of oxygen were less efficient in initiating HDL oxidation than in the presence of oxygen (action of .OH/O(.-)2 free radicals), which was in agreement with the enhancement of the action of .OH free radicals by oxygen. The remaining significant level of vitamin E in HDLs at high radiation doses in the absence of oxygen could be explained by a regeneration of vitamin E by an oxidation product that was able to reduce the alpha-tocopheroxyl radical. The yields related to the decrease in the vitamin E content of HDLs after exposure to radiation with .OH or .OH/O(.-)2 free radicals were slightly higher than those obtained previously in LDLs under similar experimental conditions. Moreover, in the presence of oxygen, .OH free radicals led to a lower formation of thiobarbituric acid-reactive substances in HDLs than in LDLs. Such discrepancies in the behavior of these two lipoprotein fractions could be related to the differences in the chemical composition of HDLs and LDLs.
Radiation Research | 2001
Dominique Bonnefont-Rousselot; Annick Rouscilles; Catherine Bizard; Jacques Delattre; Daniel Jore; Monique Gardès-Albert
Abstract Bonnefont-Rousselot, D., Rouscilles, A., Bizard, C., Delattre, J., Jore, D. and Gardès-Albert, M. Antioxidant Effect of Ethanol toward In Vitro Peroxidation of Human Low-Density Lipoproteins Initiated by Oxygen Free Radicals. This study was designed to evaluate the effect of ethanol on the peroxidation of human low-density lipoprotein (LDL) initiated by oxygen free radicals (O2·– and ·OH in the absence of ethanol; O2·– and ethanol-derived peroxyl radicals, RO2·, in the presence of ethanol) generated by γ radiolysis. Initial radiolytic yields as determined by several markers of lipid peroxidation [i.e. decrease in endogenous antioxidants α-tocopherol and β-carotene, formation of conjugated dienes and of thiobarbituric acid-reactive substances (TBARS)] were determined in 3 g liter−1 LDLs (expressed as total LDL concentration) in the absence of ethanol or its presence at six different concentrations (0.42–17 × 10−2 mol liter−1). Ethanol acted as an antioxidant by decreasing the rate of consumption of LDL endogenous antioxidants and the yields of formation of lipid peroxidation products, and by delaying the onset of the propagation phase for conjugated dienes and TBARS. With regard to the different markers studied, except for α-tocopherol and β-carotene consumption, the effect of ethanol did not appear to be dependent on its concentration. Indeed, ·OH were scavenged by ethanol at the lowest ethanol concentration (0.42 × 10−2 mol liter−1), leading to RO2·. These RO2· resulted in lower radiation-induced yields related to endogenous antioxidant consumption or to formation of lipid peroxidation products (for example, approximately 10% of RO2· oxidized LDLs from TBARS). Thus, under our in vitro conditions, ethanol behaved as an antioxidant when added to the LDL solutions. This should be taken into account in the reported antioxidant activity of wine. This is also of interest when lipophilic compounds have to be added as ethanolic solutions to LDLs to evaluate in vitro their antioxidant activity toward LDL peroxidation.
Radiation Research | 1999
Dominique Bonnefont-Rousselot; Christine Segaud; Daniel Jore; Jacques Delattre; Monique Gardès-Albert
This study was designed to evaluate the antioxidant effect of probucol on peroxidation of low-density lipoproteins (LDLs) initiated by oxygenated free radicals (O2*-) and ethanol-derived peroxyl radicals (RO2*) generated by gamma radiolysis. Initial radiolytic yields related to the markers of lipid peroxidation [i.e. decrease in endogenous alpha-tocopherol, formation of thiobarbituric acid-reactive substances (TBARS) and conjugated dienes] were determined as a function of LDL concentration (1.5 and 3 g l(-1), expressed as total LDL) and in the absence or the presence of probucol at different concentrations (2.3 x 10(-6), 3.5 x 10(-6), 9 x 10(-6) and 20.5 x 10(-6) mol l(-1)). Our results showed that probucol was able to decrease not only the yields of TBARS and conjugated dienes but also the levels of these peroxidation products obtained at high doses (2500 Gy) compared to LDLs without probucol. Under our conditions, probucol displayed an optimal antioxidant effect for an initial concentration in LDLs equivalent to 15 probucol molecules per LDL particle, which corresponded to a pharmacologically relevant concentration of probucol. Moreover, our data showed that probucol was unable to react with RO2* and thus did not protect LDL vitamin E from free radical attack. In addition, the scavenging capacity of probucol on O2*- appeared to be very poor, and probucol more likely reacted with LDL intermediate radical products. Finally, a very significant steady-state level of probucol remained in LDLs at high doses (up to 2500 Gy), equivalent to at least 40% of the initial concentration of probucol. This addressed the question of a mechanism for regeneration of probucol in LDLs. Our results as a whole suggested that the antioxidant effect of probucol in vivo could not be explained by its scavenging capacity with regard to RO2*/O2*- free radicals.
Radiation Research | 2000
J. Hindo; C. Hauville; S. Rémita; P. Thérond; Martine Couturier; Daniel Jore; M. Gardes-Albert
Abstract Hindo, J., Hauville, C., Rémita, S., Thérond, P., Couturier, M., Jore, D. and Gardès-Albert, M. Evidence of the Formation of Different Hydroperoxides in Irradiated Gamma-Linolenate Solutions: Effect of Micelle Formation. Radiat. Res. 153, 201–207 (2000). Peroxidation of unconjugated polyunsaturated fatty acids such as linolenic acid proceeds through a free radical chain mechanism and is accompanied by the formation of conjugated dienes such as hydroperoxides. In an investigation of radiation-induced oxidation of aqueous linolenate, we have measured two indexes of peroxidation: (1) conjugated dienes by means of absorption spectroscopy and (2) hydroperoxides by high-pressure liquid chromatography using detection of chemiluminescence. The experimental results indicate a strong effect of the concentration of linolenate on the yields of oxidized products. In addition, this work shows the quantitative production of two kinds of hydroperoxides. The ratio of these hydroperoxides is independent of the radiation dose but is dependent on the linolenate concentration. One hydroperoxide is formed predominantly below the critical micellar concentration (3 mM under our conditions), while the second is observed predominantly when micelles are formed in the aqueous medium. The influence of the composition of the medium on the nature of both hydroperoxides is discussed.
Journal of Pineal Research | 2007
Jamila Mekhloufi; Heidi Vitrac; Said Yous; Patrick Duriez; Daniel Jore; Monique Gardès-Albert; Dominique Bonnefont-Rousselot
Abstract: This study assessed the location of melatonin (N‐acetyl‐5‐methoxytryptamine) and of a pinoline derivative (GWC22) [6‐ethyl‐1‐(3‐methoxyphenyl)‐2‐propyl‐1,2,3,4‐tetrahydro‐beta‐carboline], when present in lipid assemblies such as linoleate micelles, phosphatidylcholine liposomes or low density lipoproteins (LDL). The efficiency of radical scavenging by these compounds is highly dependent on their partitioning between the lipidic and aqueous phases. We determined the proportion of melatonin or GWC22 in the aqueous and lipid phases of each system (concentrations of the antioxidants ranging between 3 × 10−5 and 10−4 m) by assaying melatonin or GWC22 by HPLC/UV detection, or by fluorescence for melatonin in micelles. Our results show that melatonin and GWC22 were preferentially located in the aqueous phase of micelles (68.4% and 59.0%, respectively), whereas only 30.5% of melatonin and 39.0% of GWC22 were found in the lipid phase. By contrast, in phosphatidylcholine liposomes, both compounds were essentially present in the lipid phase (73.5% for melatonin and 79.1% for GWC22, versus 25.9% and 19.5% in the aqueous phase, respectively). In the case of LDL, 99.9% of the melatonin added was found in the methanol/water extracting phase containing phospholipids, unesterified cholesterol and apolipoprotein B100. The partitioning of melatonin and GWC22 in linoleate micelles gave new insights on the marked protective effect of GWC22 towards radiation‐induced lipid peroxidation and allowed us to determine more accurately the lower limit values of the reaction rate constants of the two molecules studied with lipid peroxyl radicals, i.e. k(LOO•+melatonin) ≥ 9.0 × 104m−1s−1 and k(LOO•+GWC22) ≥ 3.5 × 105m−1s−1.
Radiation Research | 1998
C. Hauville; S. Rémita; P. Thérond; A. Rouscilles; Martine Couturier; Daniel Jore; M. Gardes-Albert
Peroxidation of polyunsaturated fatty acids such as linoleic acid in aqueous micellar solution proceeds through a free-radical chain mechanism and is accompanied by the formation of conjugated dienes, some in the form of hydroperoxides. In the course of an investigation of radiation-induced oxidation of aqueous sodium linoleate, we have measured three indexes of peroxidation-conjugated dienes, hydroperoxides and thiobarbituric acid-reactive substances-by means of absorption spectroscopy, high-pressure liquid chromatography and spectrofluorimetry, respectively. There are linear correlations between the amounts of conjugated dienes, hydroperoxides and thiobarbituric acid-reactive substances. The radiolytic yields have been determined from the radiation dose dependence of the three markers of peroxidation as a function of sodium linoleate concentration. The results obtained indicate a strong effect of the concentrations of oxygen and linoleate on the yields of the products. The yields at different lipid concentrations display a large increase in chain propagation length; this is discussed in terms of the effect of micellar size.
Redox Report | 2003
Dominique Bonnefont-Rousselot; Virginie Guilloz; Sylvie Lepage; Catherine Bizard; Patrick Duriez; Daniel Lesieur; Jacques Delattre; Daniel Jore; Monique Gardès-Albert
Abstract This study was designed to evaluate the effect of high concentrations of melatonin on the peroxidation of human low density lipoproteins (LDLs) initiated by O2•- and ethanol-derived peroxyl radicals (RO2•) from water gamma radiolysis in the presence of ethanol. LDL (3 g/l; total LDL concentration) was oxidized in the absence of melatonin or in its presence at three concentrations (50 × 10-6, 100 × 10-6 or 250 × 10-6 mol/l) in ethanol. Radiolytic yields (i.e. number of mole consumed or produced per Joule) of the markers of lipid peroxidation were determined (i.e. decrease in the endogenous antioxidants α-tocopherol and β-carotene, formation of conjugated dienes and of thiobarbituric acid-reactive substances [TBARS]). Melatonin decreased the yields of lipid peroxidation products and delayed the onset of the propagation phase for conjugated dienes and TBARS in a concentration-dependent manner. Nevertheless, melatonin did not protect endogenous α-tocopherol against peroxyl-induced oxidation (probably due to a lower scavenging capacity than that of α-tocopherol towards peroxyl radicals), but delayed the consumption of LDL endogenous β-carotene and decreased its rate of disappearance. The effect of melatonin seemed to be the highest for a melatonin concentration of 250 × 10-6 mol/l.
Radiation Research | 2000
Driss Lisfi; Dominique Bonnefont-Rousselot; Marie Fernet; Daniel Jore; Jacques Delattre; Monique Gardès-Albert
Abstract Lisfi, D., Bonnefont-Rousselot, D., Fernet, M., Jore, D., Delattre, J. and Gardès-Albert, M. Protection of Endogenous Vitamin E and Beta-Carotene by Aminoguanidine upon Oxidation of Human Low-Density Lipoproteins by ·OH/O2·−. This study was designed to evaluate the antioxidant effect of aminoguanidine toward human low-density lipoproteins (LDLs) initiated by oxygenated free radicals (·OH/O2·−) generated by gamma radiolysis. Initial radiolytic yields related to the markers of lipid peroxidation [i.e. decrease in endogenous α-tocopherol and β-carotene, formation of thiobarbituric acid-reactive substances (TBARS) and conjugated dienes] were determined in 3 g liter−1 LDLs (expressed as total LDL concentration) in the absence and presence of 10 different concentrations of aminoguanidine (from 0.04 to 5 mmol liter−1). Fluorescence and relative electrophoretic mobility of oxidized LDLs were also studied as markers that indirectly reflect the attack of the protein moiety of LDLs (namely apolipoprotein B). Our data clearly showed the inhibitory effect of aminoguanidine on lipid peroxidation induced in LDLs by ·OH/O2·− in a concentration-dependent manner. This effect probably resulted from a scavenging activity of aminoguanidine toward ·OH. In contrast, aminoguanidine did not appear to react significantly with O2·−, which resulted in a poor residual lipid peroxidation. Our data led us to determine an optimum [aminoguanidine]/[LDL] ratio ranging from 250 to 500 to obtain the best in vitro protection of LDLs under our experimental conditions. It is also of great interest that aminoguanidine was able to protect endogenous α-tocopherol and β-carotene of LDLs upon ·OH/O2·−-induced oxidation.