Abstract

The aim of this study was to evaluate the mutagenicity (clastogenicity/aneugenicity) of a glycolic extract of Ziziphus joazeiro bark (GEZJ) by the micronucleus assay in mice bone marrow. Antimutagenic activity was also assessed using treatments associated with GEZJ and doxorubicin (DXR). Mice were evaluated 24-48 h after exposure to positive (N-nitroso-N-ethylurea, NEU - 50 mg.kg(-1) and DXR - 5 mg.kg(-1)) and negative (150 mM NaCl) controls, as well as treatment with GEZJ (0.5-2 g.kg(-1)), GEZJ (2 g.kg(-1)) + NEU and GEZJ (2 g.kg(-1)) + DXR. There were no significant differences in the frequencies of micronucleated polychromatic erythrocytes in mice treated with GEJZ and GEJZ + DXR compared to the negative controls, indicating that GEZJ was not mutagenic. Analysis of the polychromatic:normochromatic erythrocyte ratio revealed significant differences in the responses to doses of 0.5 g.kg(-1) and 1-2 g.kg(-1) and the positive control (NEU). These results indicated no systemic toxicity and moderate toxicity at lower and higher doses of GEZJ. The lack of mutagenicity and systemic toxicity in the antimutagenic assays, especially for treatment with GEZJ + DXR, suggested that phytochemical compounds in Z. joazeiro bark attenuated DXR-induced mutagenicity and the moderate systemic toxicity of a high dose of Z. joazeiro bark (2 g.kg(-1)). Further studies on the genotoxicity of Z. joazeiro extracts are necessary to establish the possible health risk in humans and to determine the potential as a chemopreventive agent for therapeutic use.

Highlights

  • Many species of medicinal plants, such as Amburana cearensis, Anadenanthera colubrina, Mentha x villosa, Myracrodruon urundeuva, Plectranthus amboinicus, Ruta graveolens, Ximenia americana and Ziziphus joazeiro, are widely used by communities in the Brazilian Caatinga to treat a large spectrum of clinical conditions ranging from diseases requiring palliative care to general aches, e.g., bronchitis, sinusitis, rhinitis, nasal congestion, headaches, flu, fever, expectorant, colic, hypertension, thrombosis, indigestion, intestinal dysfunction, liver and kidney problems, infectious and inflammatory processes and pain in general (Cartaxo et al, 2010)

  • These results suggest absence of mutagenicity for glycolic extract of Ziziphus joazeiro bark (GEZJ), regardless of the extract dose and time interval, the responses varied between sexes

  • GEJZ (2 g.kg-1) showed antimutagenic activity towards the chemotherapeutic agent DXR (5 mg.kg-1) or NEU (50 mg.kg-1), regardless of the time interval, once again intersex variation was observed. These findings indicate that compounds in GEZJ can act against DXRinduced mutagenic effects in mouse bone marrow

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Summary

Introduction

Many species of medicinal plants, such as Amburana cearensis, Anadenanthera colubrina, Mentha x villosa, Myracrodruon urundeuva, Plectranthus amboinicus, Ruta graveolens, Ximenia americana and Ziziphus joazeiro, are widely used by communities in the Brazilian Caatinga to treat a large spectrum of clinical conditions ranging from diseases requiring palliative care to general aches, e.g., bronchitis, sinusitis, rhinitis, nasal congestion, headaches, flu, fever, expectorant, colic, hypertension, thrombosis, indigestion, intestinal dysfunction, liver and kidney problems, infectious and inflammatory processes and pain in general (Cartaxo et al, 2010). (Rhamnaceae) is a native Brazilian tree resistant to dry environments (Cartaxo et al, 2010). This species is an important source of water and food for animals in arid habitats (Braga, 1960; Cruz, 1985; Nunes et al, 1987). A phytochemical analysis of Z. joazeiro Mart. A similar analysis of a dichloromethane extract of Z. joazeiro Mart. Bark identified triterpenoids with weak antibacterial activity (e.g., betulinic, alphitolic and ursolic acids) and remarkable activity against Staphylococcus epidermidis [e.g., betulinic acid ester derivatives such as 7b-(4hydroxy-benzoyloxy), 7b-(4-hydro-3-methoxy-benzoyloxy) and 27-(4-hydroxy-3-methoxy-benzoyloxy)] (Schuhly et al, 1999). Experimental studies have identified potential antifungal (Cruz et al, 2007), antibacterial (Schuhly et al, 1999; Alviano et al, 2008; Leal et al, 2010), antioxidant (Alviano et al, 2008) and antipyretic (Nunes et al, 1987) activities, as well as low toxicity (Alviano et al, 2008)

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