Laboratório de Farmacogenômica e Biologia Molecular , Faculdade de Ciências Médicas , Universidade José do Rosário Vellano , Alfenas, MG , Brazil . ; Centro de Pesquisa e Pós-Graduação em Ciência Animal , Área de Patologia e Farmacologia Animal , Universidade José do Rosário Vellano , Alfenas, MG , Brazil .
Departamento de Ciências Exatas , Escola de Agricultura "Luiz de Queiroz" , Universidade de São Paulo , Piracicaba, SP , Brazil .
Genet Mol Biol. 2014 Jun;37(2):428-38. doi: 10.1590/s1415-47572014000300016.
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.
本研究旨在通过小鼠骨髓微核试验评估枳椇树皮醇提物(GEZJ)的致突变性(断裂/致畸性/变异性)。还使用与 GEZJ 和阿霉素(DXR)相关的处理方法评估了抗突变活性。在暴露于阳性对照(N-亚硝基-N-乙基脲,NEU-50mg.kg(-1)和 DXR-5mg.kg(-1))和阴性对照(150mMNaCl)以及用 GEZJ(0.5-2g.kg(-1))、GEZJ(2g.kg(-1))+NEU 和 GEZJ(2g.kg(-1))+DXR 处理后 24-48 小时,对小鼠进行了评估。与阴性对照相比,用 GEJZ 和 GEJZ+DXR 处理的小鼠的微核多染红细胞频率没有显着差异,表明 GEZJ 没有致突变性。多染性:正常红细胞比的分析表明,在 0.5g.kg(-1)和 1-2g.kg(-1)剂量以及阳性对照(NEU)下,反应有显着差异。这些结果表明,GEZJ 的低剂量和高剂量均没有全身毒性,只有中度毒性。在抗突变试验中,缺乏致突变性和全身毒性,尤其是在使用 GEZJ+DXR 时,表明枳椇树皮中的植物化学化合物减轻了 DXR 诱导的突变性和高剂量枳椇树皮(2g.kg(-1))的中度全身毒性。需要进一步研究枳椇提取物的遗传毒性,以确定其对人类的潜在健康风险,并确定其作为治疗用途的化学预防剂的潜力。