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In-Depth Information
stage of the studies is difficult to assure
that
Z. punctata
and the chalcone are anti-
carcinogens.
both in the intestine and stomach leading to
lesions that morphologically resemble those
induced by ethanol (Parks
et al
., 1983; Itoh
and Guth, 1985). Recently, the pineal hor-
mone melatonin was shown to scavenge
both the hydroxyl and peroxyl radicals
(Tan
et al
., 1993; Pieri
et al
., 1994; Poeggeler
et al
., 1995). Both
in vitro
and
in vivo
stud-
ies have demonstrated the antioxidant prop-
erties of melatonin (Hardeland
et al
., 1995;
Reiter, 1995; Reiter
et al
., 1995).
The intragastric administration of
2¢,4¢-dihydroxychalcone or 2¢,4¢-dihydroxy-
3¢-methoxychalcone (100 mg/kg, orally)
inhibited both gastric and duodenal lesions
induced by ethanol in rats in different
degrees, but pre-treatment with melatonin
(10 mg/kg, orally) increased the cytoprotec-
tive effect. Hydroxychalcones, with an
ample distribution in the plant kingdom,
prevent gastric mucosal lesion formation
induced by oral administration of severe
necrotizing agents, such as 60% ethanol in
150 mM HCl and 0.2N NaOH, suggesting
that these compounds possess a potent cyto-
protective property on the gastric mucosa
(Yamamoto
et al
., 1992). The mechanisms
responsible for the apparent additive action
of the chalcones and melatonin need to be
explained. These effects could be due, in
part, to the radical scavenging activity of the
melatonin (Reiter
et al
., 1995).
12.4.4
Cytoprotective effect
The pharmacological effect of aerial parts of
Z. punctata
extracts (infusion and acetone
extract) and 2¢,4¢-dihydroxychalcone and
2¢,4¢-dihydroxy-3¢-methoxychalcone on the
gastrointestinal tract of mice and rats was
evaluated through the study of the induc-
tion of gastric lesions (Ortega
et al
., 2003).
Oral administration of absolute ethanol was
used as necrotizing agent (Robert
et al
.,
1979) to induce gastric lessions. The degree
of erosion in the glandular part of the stom-
ach was analysed (Guardia
et al
., 1994).
Ethanol produced gastric ulcers in all the
animals treated. Pretreatment with
Z. punc-
tata
infusion (10% at a dose of 50 ml/kg,
orally), acetone extract (250 mg/kg, orally)
and the isolated compounds (100 mg/kg in
0.4% carboxymethyl cellulose, orally) pro-
tected against gastric ulceration. Another
important property of these products is the
delay in the transit by the small intestine
produced by the ingestion of castor oil as a
cathartic agent, suggesting their use as an
antidiarrhoeal substance. The data available
indicate that extracts of
Z. punctata
and its
purified compounds can be used to reduce
the intestinal transit in rats and mice and as
protective agents against ethanol-induced
stomach ulceration in rats. The action of
melatonin on the cytoprotective effect of
chalcones from
Z. punctata
was assayed on
ethanol-induced gastroduodenal injury in
rats (de la Rocha
et al
., 2003). In previous
studies it was suggested that one of the
mechanisms responsible for ethanol-
induced gastroduodenal damage is the gen-
eration of free radicals (Pihan
et al
., 1987;
Szelenyi and Brune, 1988). Compounds with
free-radical scavenging properties, such as
thiourea, dimethylsulfoxide and sulfydryl-
containing substances, significantly reduce
ethanol toxicity to gastric mucosa. Also,
oxygen-derived free radicals have been
shown to participate in reperfusion damage
12.4.5
Antioxidative activity and DNA
protection
Living cells are permanently exposed to
potentially damaging free radicals of intra-
cellular origin, such as those arising from
normal cellular metabolism, or extracellu-
lar, originating as consequence, for instance,
of exposure to ultraviolet or ionizing radia-
tions. Of special interest are the reactive
oxygen species (ROS), including the highly
reactive hydroxyl radical (HO
•
), superoxide
radical (O
2
•−
), and non-radical hydrogen
peroxide (H
2
O
2
). The cellular targets for oxi-
dative modification by ROS include DNA,
lipids and proteins (Mantena
et al
., 2008).
Consequently, the ingestion of antioxidants
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