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.