Inhibitory effects of lemon grass (Cymbopogon citratus Stapf) on formation of azoxymethane-induced DNA adducts and aberrant crypt foci in the rat colon |
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Authors: | Suaeyun R; Kinouchi T; Arimochi H; Vinitketkumnuen U; Ohnishi Y |
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Institution: | Department of Bacteriology, School of Medicine, The University of Tokushima, Kuramoto-cho, Japan. |
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Abstract: | The 80%-ethanol extract of lemon grass (Cymbopogon citratus Stapf), a
medicinal plant in Thailand, has been reported to be antimutagenic against
various known mutagens in the Salmonella mutation assay. To investigate
chemoprevention in an animal carcinogenesis model, we examined inhibitory
effects of the lemon grass extract on the formation of azoxymethane
(AOM)-induced DNA adducts and aberrant crypt foci (ACF) in the rat colon.
One week after the start of the treatment with lemon grass extract at doses
of 0.5 or 5 g/kg body wt by gavage, F344 rats received two s.c. injections
of 15 mg of AOM per kg body weight at 1 week apart. For DNA adduct analysis
of the colon and liver, the rats were killed 12 h after the second AOM
injection. The DNA from the liver and colon were used for O6-methylguanine
and N7-methylguanine analysis. For ACF analysis in the initiation stage,
AOM-injected rats were continuously treated with lemon grass extract and
were killed 3 weeks after the second AOM injection. For analysis in the
promotion stage the treatment with the lemon grass extract (0.5 g/kg)
started 2 weeks after the second AOM injection and continued for 12 weeks
until the animals were killed. Lemon grass treatment significantly
inhibited DNA adduct formation in both the colonic mucosa and the muscular
layer but not in the liver. In addition, lemon grass extract treatment
significantly inhibited ACF formation in both the initiation stage and the
promotion stage. Especially in the promotion stage, lemon grass treatment
inhibited the formation of larger ACF (with four or more crypts per focus),
which was predictive of tumor incidence. Furthermore, lemon grass extract
inhibited fecal beta-glucuronidase competitively and had antioxidant
activity. These results suggest that the lemon grass extract inhibits the
release of activated aglycon, methylazoxymethanol, from a glucuronide
conjugate in the colon, and decreases the DNA adducts and ACF formation in
the rat colon.
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