Genotoxicity evaluation of kaurenoic acid, a bioactive diterpenoid present in Copaiba oil

Copaiba oil extracted from the Amazon traditional medicinal plant Copaifera langsdorffii is rich in kaurenoic acid (ent-kaur-16-en-19-oic acid), a diterpene that has been shown to exert anti-inflammatory, hypotensive, and diuretic effects in vivo and antimicrobial, smooth muscle relaxant and cytotoxic actions in vitro. This study evaluated its potential genotoxicity against Chinese hamster lung fibroblast (V79) cells in vitro, using the Comet and the micronucleus assays. Kaurenoic acid was tested at concentrations of 2.5, 5,10, 30 and 60 μg/mL. The positive control was the methylmethanesulfonate (MMS). The duration of the treatment of V79 cells with these agents was 3 h. The results showed that unlike MMS, kaurenoic acid (2.5, 5, and 10 μg/mL) failed to induce significantly elevated cell DNA damage or the micronucleus frequencies in the studied tests. However, exposure of V79 cells to higher concentrations of kaurenoic acid (30 and 60 μg/mL) caused significant increases in cell damage index and frequency. The data obtained provide support to the view that the diterpene kaurenoic acid induces genotoxicity.