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Full Length Research Paper
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Assessment
of anticlastogenic activity of cinnamic acid:
Anticlastogenic index (ACI) and model simulation
Ahmed M. El-Shehawi1,2*,
Mostafa A. Eldakak2
and
Mohamed
A. Seehy2
1Department of
Biotechnology, Taif University, Taif, Saudi Arabia.
2Department of Genetics,
University of Alexandria, Elshatby, Alexandria, Egypt.
*Corresponding author. E-mail:
elshehawi@hotmail.com.
Tel: 0554904625.Fax: 0966027367409.
Abbreviations: CA,
Cinnamic acid; PCE,
polychromatic erythrocytes;
MI, mitotic index; ACI, anticlastogenic index;
CMA,
chlormadinone acetate;
NDGA,
nordihydroguaiaretic acid.
Accepted 9 June, 2011 |
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Abstract |
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Cinnamic acid and its derivatives are an important member of
the
phenolic compound used in food supplements. They usually occur
in various conjugated forms, more frequently esters and
glycosides. Mice (Mus musculus, 2n = 40) were employed as
an experimental mammalian system to assess the anticlastogenic
activity of cinnamic acid (CA) induced by Endoxan. Four doses;
1/32, 1/16, 1/8 and 1/4 of the LD50 of CA (5, 10, 20
and 40 mg/kg, respectively) in combination with five
administration times of CA were tested. Micronucleated
polychromatic erythrocytes (PCE) and mitotic index (MI) were
used as a sensitive short term genotoxic bioassays. The results
obtained showed that low doses (1/32 LD50 and 1/16 LD50)
decreased the percentage of PCE significantly compared with that
of the positive control and closer to that of the negative
control. The data of this study were used to calculate a new
index called anticlastogenic index (ACI). The new index measures
the anticlastogenic activity of a compound or an extract. The
ACI beside the percentage of PCE can give a deeper look of the
anticlastogenic activity of compounds. It also makes it easy to
draw conclusions from the genotoxicity data. The maximum ACI of
CA was achieved when both CA and Endoxan were given
concurrently. On the other hand, the higher doses of CA (1/8 and
1/4 LD50) caused a significant increase in
the
percentage of PCE. This gives evidence that CA at high doses (20
and 40 mg/kg) would be considered as a positive clastogen
itself. CA significantly decreased the mitotic index compared
with the negative control. In addition, high doses showed sharp
decrease in mitotic index. Direct significant correlation
coefficient was found between the ACI and the mitotic index. The
data also were used for
the
simulation of a model to
predict the ACI of doses with different relative timing to a
treatment of the clastogen that were not conducted
experimentally in the limit of experiment data range.
Key words:
Anticlastogenic, cinnamic acid, anticlastogenic index, ACI,
mitotic index, mice, model simulation of ACI. |