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

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.

Vernonanthura polyanthes leaves aqueous extract enhances doxorubicin genotoxicity in somatic cells of Drosophila melanogaster and presents no antifungal activity against Candida spp.

“…The extract of organic tomato Lycopersicon esculentum when combined with DXR also potentiates the genotoxic effect of this drug (Dutra et al, 2009). T. impetiginosa alone did not act as a genotoxin or an antigenotoxin, but it induced the DXR genotoxicity when associated with this mutagen (Sousa et al, 2009). Moreover, it was demonstrated, using micronucleus assay, that hydroalcoholic extract of Mikania glomerata (Asteraceae) aerial parts significantly increased DXR genotoxicity (Barbosa et al, 2012).…”

“…Interestingly, this enzyme complex is also responsible for DXR detoxification (Niitsu et al, 2000). It is proposed that plant components could (i) directly interact with cytochrome P450 enzymes involved in DXR metabolism or (ii) generate oxygen free radicals that could increase this enzymatic activity, both contributing to DXR mutagenicity enhancing (Sousa et al, 2009). In that way, the V. polyanthes extract used in this work may contain compound(s) that influence the DXR genotoxicity.…”

Reduction of doxorubicin-induced genotoxicity by Handroanthus impetiginosus in mouse bone marrow revealed by micronucleus assay

“…However, the authors indicated that the plant had a low toxicity profile (De Miranda et al, 2001). The genotoxic potential of H. impetiginosus bark and stem and its association with the reference mutagen DXR (antigenotoxic effects) were evaluated using a wing spot test in Drosophila melanogaster (Somatic Mutation and Recombination Test -SMART) using the standard (ST) version to evaluate direct action and the high bioactivation (HB) version to evaluate indirect action (De Sousa et al, 2009). The bark and stem of H. impetiginosus were toxic at a higher concentration (40% w/w), but did not induce Table 1.…”

“…Although numerous studies have supported the effectiveness of different forms of the crude extract of H. impetiginosus or its phytochemical compounds alone, few recent studies aimed to understand their genotoxic and mutagenic effects (Vanni et al, 1998;De Sousa et al, 2009;Lemos et al, 2012;Zabka et al, 2013). To contribute to information about the genotoxic potential of herbal and natural products, the present study evaluated the genotoxic effects (clastogenicity and aneugenicity) of the lyophilized tincture of H. impetiginosus bark in the bone marrow of mice using a micronucleus assay.…”

“…That is, H. impetiginosus alone neither acted as a genotoxin nor exerted any antigenotoxic effects on spontaneous DNA lesions. However, H. impetiginosus displayed a considerable potentiating effect on DXR genotoxicity (0.125 mg/ml) that was inversely proportional to the concentration applied (10%, 20%, and 40% w/w), indicating a dose-response relationship with toxicity (De Sousa et al, 2009). In other studies, the genotoxic activities of the hydroalcoholic extract of H. impetiginosus inflorescences were assessed using a comet assay [Single Cell-Gel Electrophoresis (SCGE)]…”