Modulatory effects of Tabebuia impetiginosa (Lamiales, Bignoniaceae) on doxorubicin-induced somatic mutation and recombination in Drosophila melanogaster

Neila C De Sousa,Warwick E Kerr,Alexandre A.A De Rezende,Ulrich Graf,Zaira R Guterres,Regildo M.G Da Silva,Mário A Spanó

doi:10.1590/s1415-47572009005000042

Neila C De Sousa, Warwick E Kerr + Show 5 more

Open Access

https://doi.org/10.1590/s1415-47572009005000042

Copy DOI

Abstract

The wing Somatic Mutation and Recombination Test (SMART) in D. melanogaster was used to study genotoxicity of the medicinal plant Tabebuia impetiginosa. Lapachol (naphthoquinone) and β-lapachone (quinone) are the two main chemical constituents of T. impetiginosa. These compounds have several biological properties. They induce apoptosis by generating oxygen-reactive species, thereby inhibiting topoisomerases (I and II) or inducing other enzymes dependent on NAD(P)H:quinone oxidoreductase 1, thus affecting cell cycle checkpoints. The SMART was used in the standard (ST) version, which has normal levels of cytochrome P450 (CYP) enzymes, to check the direct action of this compound, and in the high bioactivation (HB) version, which has a high constitutive level of CYP enzymes, to check for indirect action in three different T. impetiginosa concentrations (10%, 20% or 40% w/w). It was observed that T. impetiginosa alone did not modify the spontaneous frequencies of mutant spots in either cross. The negative results observed prompted us to study this phytotherapeuticum in association with the reference mutagen doxorubicin (DXR). In co-treated series, T. impetiginosa was toxic in both crosses at higher concentration, whereas in the HB cross, it induced a considerable potentiating effect (from ~24.0 to ~95.0%) on DXR genotoxity. Therefore, further research is needed to determine the possible risks associated with the exposure of living organisms to this complex mixture.

Highlights

Tabebuia impetiginosa (Lamiales, Bignoniaceae), popularly known as Ipê, pau d’arco, pink trumpet tree, taheebo and lapacho rosado, is a medicinal plant, native to tropical rain forests and the ‘cerrado’ throughout Central and South America
The commercial preparation of the powdered bark and stem of T. impetiginosa was submitted to a dose-range test, which demonstrated that T. impetiginosa presented toxicity in larvae fed for 48 h
No significant differences in the frequency of mutant spots were observed among flies treated with all the T. impetiginosa concentrations and the negative control in ST and high bioactivation (HB) crossbreeds marker trans-heterozygous (MH) flies

Summary

Introduction

Tabebuia impetiginosa (Lamiales, Bignoniaceae), popularly known as Ipê, pau d’arco, pink trumpet tree, taheebo and lapacho rosado, is a medicinal plant, native to tropical rain forests and the ‘cerrado’ (savannah) throughout Central and South America. The bark of the Tabebuia spp stem is a source of furanonaphthoquinones, quinines, naphthoquinones, ben-. Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphtalene-dione], naphthoquinone and its derivative b-Lapachone (2,2-dimethyl-3,4-dihydro-2,4-benzo[h]chromene-5,6-dione), which possess biologically active properties, can be isolated from T. impetiginosa (Park et al, 2003). The inner bark extract of this plant potently inhibited cell proliferation and DNA synthesis (Son et al, 2006). The stereo-selective synthesis of biologically active naphthoquinones from Tabebuia avellanedae, as described by Yamashita et al (2007), displayed potent cytotoxicity against several human tumor cell lines, whereas it showed lower cytotoxicity against certain normal human cell lines when compared with that of mitomycin. A synthetic version of the natural product b-lapachone has been isolated from T. impetiginosa, and has demonstrated promising anticancer activity (Savage et al, 2008)

Objectives

Methods

Results

Conclusion