title: Melatonin related compounds inhibit lipid peroxidation during copper or free radical-induced LDL oxidation.
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 (RO(2)(*))] 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-beta-carboline (GWC20) which is a pinoline derivative. Their effects were compared with those of melatonin at the same concentration (100 micromol/L). None of the three tested compounds protected endogenous LDL alpha-tocopherol from oxidation by RO(2)(*)/O(2)(*)- free radicals. By contrast, they all protected beta-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.
authors.affiliation: Laboratoire de Biochimie, Hôpital de la Salpêtrière (AP-HP), Paris, France. dominique.rousselot@psl.ap-hop-paris.fr
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnefont-Rousselot
authors.forename: Gwénaël
authors.initials: G
authors.lastname: Chevé
authors.forename: Andrea
authors.initials: A
authors.lastname: Gozzo
authors.forename: Anne
authors.initials: A
authors.lastname: Tailleux
authors.forename: Virginie
authors.initials: V
authors.lastname: Guilloz
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Caisey
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Teissier
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Fruchart
authors.forename: Jacques
authors.initials: J
authors.lastname: Delattre
authors.forename: Daniel
authors.initials: D
authors.lastname: Jore
authors.forename: Daniel
authors.initials: D
authors.lastname: Lesieur
authors.forename: Patrick
authors.initials: P
authors.lastname: Duriez
authors.forename: Monique
authors.initials: M
authors.lastname: Gardès-Albert
mesh_terms: D000975:Antioxidants; D001549:Benzamides / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D005609:Free Radicals / Q000494:pharmacology*; D005720:Gamma Rays; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D008550:Melatonin / Q000494:pharmacology* / Q000502:physiology; D010084:Oxidation-Reduction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001549:Benzamides; D002243:Carbolines; D005609:Free Radicals; C470988:GWC20; D007211:Indoles; D008077:Lipoproteins, LDL; C470989:N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-3,5-di-tert-butyl-4-hydroxybenzamide; D017392:Thiobarbituric Acid Reactive Substances; D019207:beta Carotene; D014810:Vitamin E; D003300:Copper; D008550:Melatonin