title: (-)-Hinokinin causes antigenotoxicity but not genotoxicity in peripheral blood of Wistar rats.
abstract: (-)-Hinokinin, a dibenzylbutyrolactone lignan, exhibits significant trypanocidal activity both in vitro and in vivo, and was obtained by partial synthesis from (-)-cubebin isolated from the dry seeds of Piper cubeba. Considering the good trypanocidal activity of (-)-hinokinin, as well as its potential for the development of new drugs, it is extremely important to evaluate its possible mutagenic activity to allow its safe use in humans. In the present study, we evaluated the antimutagenic effect of (-)-hinokinin on the chromosome damage induced by the chemotherapeutic agent doxorubicin (DXR). The test system employed was the analysis of micronucleated polychromatic erythrocytes in peripheral blood of Wistar rats. Additionally, the antioxidant activity of (-)-hinokinin was evaluated in in vitro experiments by measuring the production of hydrogen peroxide and other peroxides. Our results showed that animals treated with different doses of (-)-hinokinin (10, 20, and 40mg/kgb.w.) exhibited micronucleated cell frequencies similar to that of the negative control. In addition, treatment with combinations of (-)-hinokinin and DXR resulted in lower micronucleated cell frequencies than those observed for animals treated with DXR alone. The present study shows that (-)-hinokinin not only has no genotoxic effect, but is also effective in reducing the chromosome damage induced by DXR. (-)-Hinokinin exerted a significant antioxidant effect on parasite mitochondria in the protocol used, which might be one possible mechanism by which this compound may exert a protective effect on the chromosome damage induced by the free radicals generated by DXR.
authors.affiliation: Universidade de Franca, Av Dr Armando Salles Oliveira, 201-Parque Universitário, 14404-600 Franca, São Paulo, Brazil.
authors.forename: Jamile Ferraris
authors.initials: JF
authors.lastname: Medola
authors.forename: Vívian Pedigone
authors.initials: VP
authors.lastname: Cintra
authors.forename: Erika Patri Cia
authors.initials: EP
authors.lastname: Pesqueira E Silva
authors.forename: Vanessa
authors.initials: V
authors.lastname: de Andrade Royo
authors.forename: Rosângela
authors.initials: R
authors.lastname: da Silva
authors.forename: Juliana
authors.initials: J
authors.lastname: Saraiva
authors.forename: Sérgio
authors.initials: S
authors.lastname: Albuquerque
authors.forename: Jairo Kenupp
authors.initials: JK
authors.lastname: Bastos
authors.forename: Márcio Luís
authors.initials: ML
authors.lastname: Andrade E Silva
authors.forename: Denise Crispim
authors.initials: DC
authors.lastname: Tavares
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D052117:Benzodioxoles; D002869:Chromosome Aberrations; D004149:Dioxoles / Q000494:pharmacology*; D004317:Doxorubicin / Q000633:toxicity; D005260:Female; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D015162:Micronucleus Tests; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016587:Antimutagenic Agents; D052117:Benzodioxoles; D004149:Dioxoles; D017705:Lignans; C475934:hinokinin; D004317:Doxorubicin; D015107:4-Butyrolactone