ANTIOXIDANT ACTIVITY OF 5-AMINOSALICYLIC ACID AGAINST PEROXIDATION OFPHOSPHATIDYLCHOLINE LIPOSOMES IN THE PRESENCE OF ALPHA-TOCOPHEROL - ASYNERGISTIC INTERACTION
E. Goncalves et al., ANTIOXIDANT ACTIVITY OF 5-AMINOSALICYLIC ACID AGAINST PEROXIDATION OFPHOSPHATIDYLCHOLINE LIPOSOMES IN THE PRESENCE OF ALPHA-TOCOPHEROL - ASYNERGISTIC INTERACTION, Free radical research, 29(1), 1998, pp. 53-66
Oxidative damage has been implicated in the pathogenesis of inflammato
ry bowel diseases. Ei-Aminosalicylic acid (5-ASA), the anti-inflammato
ry drug commonly used in the treatment of this condition, has been sho
wn to possess antioxidant properties considered to be of particular im
portance in the pathologic context of these diseases. However, its act
ion mechanisms are far from being completely elucidated, especially re
garding its antioxidant properties in the presence of endogenous antio
xidants such as alpha-tocopherol (alpha-T), the major defence system o
f biomembranes against Lipid peroxidation. in this study we investigat
ed the scavenging activity of 5-ASA toward peroxyl radicals generated
at different sites of soybean PC liposomes, used as model membranes, e
ither alone or in combination with alpha-T. 5-ASA, separately, shows s
trong scavenging activity toward peroxyl radicals generated in the aqu
eous phase by thermal decomposition of 2,2'-azobis(2-amidinopropane hy
drochloride) (AAPH), inducing a clear concentration-dependent inhibiti
on period, either of oxygen consumption or of conjugated diene hydrope
roxides production. HPLC analysis indicates that 5-ASA is consumed, at
a constant rate, throughout the reaction, and when the inhibition per
iod is over, the oxidation late is resumed. On the other hand, apart f
rom a slight decrease in the rate of oxidation, 5-ASA is unable to sup
press efficiently lipid peroxidation, when the reaction starts inside
the lipid membranes, by thermal decomposition of 2,2'-azobis(2,4-dimet
hylvaleronitrile) (AMVN). When 5-ASA is combined with alpha-T, and the
oxidation starts in the aqueous phase, an additive inhibitory effect
occurs between both compounds. 5-ASA protects efficiently alpha-T agai
nst initial attack from AAPH-peroxyl radicals, delaying its consumptio
n. On the other hand, if the reaction starts inside the Lipid bilayer,
5-ASA prolongs significantly the inhibitory period produced by alpha-
T on the initial rate of oxidation, as measured by oxygen consumption
and conjugated diene hydroperoxides. This inhibitory effect points to
a synergistic interaction between 5-ASA and alpha-T, since 5-ASA, by i
tself, is unable to suppress the oxidation reaction. Therefore, 5-ASA
reveals an important cooperative effect with alpha-T, either affording
an efficient protection to this antioxidant compound, when free radic
als are generated in the aqueous site, or potentiating its activity wh
en oxidation is initiated inside the lipid bilayer. Taking into accoun
t that the ascorbic acid content decreases significantly in the inflam
ed mucosa of patients with inflammatory bowel diseases, our data are,
certainly, a very important contribution to the knowledge of the anti-
inflammatory action of 5-ASA.