Antioxidant Activity of Anacardic Acids - Natural Antioxidants and Biocides from Wild Medicinal Plants - page 145

as antioxidants (Arora et al ., 1998). These
transition metal ions are well known as
powerful promoters of free-radical dam-
age in both the human body (Halliwell
and Gutteridge, 1989; Henel and Linn,
1997) and foods (Aruoma and Halliwell,
1991). For example, anacardic acids may
prevent cell damage induced by H 2 O 2
because this can be converted to the more
reactive oxygen species, hydroxy radicals,
in the presence of these metal ions
(Lodovici et al ., 2001). Salicylic acid does
not have this high selectivity of chelation,
so the alk(en)yl side chain in anacardic
acids is also related to the high selectivity
towards transition metal ions. It seems
that anacardic acids act as antioxidants in
a variety ways, including inhibition of
various prooxidant enzymes involved in
the production of the reactive oxygen spe-
cies and chelate divalent metal ions such
as Fe 2+ or Cu 2+ , but do not quench reactive
oxygen species.
An antioxidant is, as a general defini-
tion, any substance capable of preventing
oxidation. Deleterious free-radical-mediated
oxidations occur in aerobic organisms as a
result of normal oxygen metabolism. Iron,
especially ferrous iron (Fe 2+ ), is able to
trigger oxidations by reducing as well as
by decomposing previously formed perox-
ides. Hence, an antioxidant that protects
from iron toxicity is a substance that can:
(i) chelate ferrous iron and prevent the
reaction with oxygen or peroxides; (ii)
chelate iron and maintain it in a redox
state that makes iron unable to reduce
molecular oxygen; and (iii) trap already
formed radicals, which is a putative action
of any substance that can scavenge free
radicals in biological systems, regardless
of whether they originate from iron-
dependent reactions or not (Fraga and
Oteiza, 2002).
The preventive antioxidant activity
of anacardic acids largely comes from
their ability to inhibit various oxidative
enzymes. It should be noted, however,
that these oxidases produce free radicals
in the human body as normal products.
Hence, anacardic acids or their metabo-
lites need to reach the sites where the

enzymes are located in living systems and
need to regulate the enzyme activity to
prevent the generation of only unneces-
sary radicals. For instance, xanthine oxi-
dase occurs almost exclusively in the
liver and small intestinal mucosa in mam-
mals. It is not clear if anacardic acids or
their metabolites can reach the site and
regulate this cellular enzyme activity. If
anacardic acids act as highly effective
xanthine oxidase inhibitors in the human
body, they can be toxic because this oxi-
dase is a normal enzyme involved in
purine metabolism. Paradoxically, xan-
thine oxidase inhibitors are useful to treat
some diseases such as gout and urate cal-
culus by regulating uric acid formation.
In any case, it seems that anacardic acids
have antioxidant activity as a result of
inhibiting oxidation-related enzymes and
these 6-alk(en)ylsalicylic acids are con-
tained in quantities in the cashew nut and
apple. Their role as antioxidants in the
human body is unknown, however, when
orally ingested, but there are several pos-
sibilities. The ingested anacardic acids
are: (i) absorbed into the system through
the intestinal tract and delivered to the
places where antioxidants are needed,
preventing the generation of unnecessary
radicals; (ii) absorbed but metabolized to
inactive forms or are not delivered to the
right places; or (iii) not absorbed and
excreted. The relevance of the in vitro
experiments in simplified systems to
in vivo protection from oxidative damage
should be carefully considered. The
results obtained indicate that further
evaluation is needed from not only one
aspect but from a whole and dynamic
perspective.

Acknowledgements

The work was presented in part at the
Symposium of Diet and the Prevention of
Gender Related Cancers in the Division of
Agricultural and Food Chemistry for the
222nd ACS National Meeting in Chicago,
Illinois.