title: Genotoxicity evaluation of kaurenoic acid, a bioactive diterpenoid present in Copaiba oil.
abstract: 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 microg/mL. The positive control was the methylmethanesulfonate (MMS). The duration of the treatment of V79 cells with these agents was 3h. The results showed that unlike MMS, kaurenoic acid (2.5, 5, and 10 microg/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 microg/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.
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: B C
authors.initials: BC
authors.lastname: Cavalcanti
authors.forename: L V
authors.initials: LV
authors.lastname: Costa-Lotufo
authors.forename: M O
authors.initials: MO
authors.lastname: Moraes
authors.forename: R R
authors.initials: RR
authors.lastname: Burbano
authors.forename: E R
authors.initials: ER
authors.lastname: Silveira
authors.forename: K M A
authors.initials: KM
authors.lastname: Cunha
authors.forename: V S N
authors.initials: VS
authors.lastname: Rao
authors.forename: D J
authors.initials: DJ
authors.lastname: Moura
authors.forename: R M
authors.initials: RM
authors.lastname: Rosa
authors.forename: J A P
authors.initials: JA
authors.lastname: Henriques
authors.forename: C
authors.initials: C
authors.lastname: Pessoa
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use / Q000633:toxicity*; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage / Q000187:drug effects*; D004224:Diterpenes / Q000627:therapeutic use / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007887:Fabaceae / Q000737:chemistry; D008175:Lung Neoplasms / Q000188:drug therapy; D008741:Methyl Methanesulfonate / Q000633:toxicity; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use / Q000633:toxicity; D014407:Tumor Cells, Cultured
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D010936:Plant Extracts; C051436:kaurenoic acid; D008741:Methyl Methanesulfonate