Human Genetics and Genetic Disorders

Statement of the Problem: Salvia officinalis is a plant species used in cooking and with many therapeutic properties, such as anti-inflammatory, antiseptic and eupeptic. Phytochemical studies of this species have identified diterpenes as their main special metabolites. Among the diterpenes of S. officinalis, manool is notable for its anti-microbial activity, chemopreventive activity in HepG2 (human hepatocarcinoma) and antiproliferative effect in different tumoral cell lines. In this sense, to better understand the action of manool on genetic material, the present study aimed to evaluate the modulating effect of diterpene on doxorubicin (DXR)induced genotoxicity in V79 cells (Chinese hamster lung fibroblast). For this purpose, the cell cultures were treated simultaneously, for three hours, with three different concentrations of manool (0.5, 1.0 and 2.0 μg/mL) and DXR (0.5 μg/mL). Negative (without treatment) and solvent (DMSO, dimethylsulfoxide, 1%) control groups were included. The micronucleus assay with blocking of the cytokinesis was used to determine the frequency of micronuclei in V79 cells submitted to the different treatments. Findings: The results showed that manool at the lowest concentration tested (0.5 μg/mL) could reduce the frequency of micronucleus induced by the mutagen. The reduction was approximately 65%. Conclusion & Significance: In view of the above, it can be concluded that manool presented a protective effect against doxorubicininduced genotoxicity. The action on free radicals or on the enzyme topoisomerase II can be possible mechanisms by which the diterpene revealed chemopreventive capacity. Furthermore, the anti-inflammatory effect proves to be involved in this preventive process, since parallel studies developed by our research group indicated that manool can significantly reduce the levels of nitric oxide produced by macrophages.