Assessment of anticlastogenic activity of cinnamic acid: Anticlastogenic index (ACI) and model simulation
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.