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Modulating effect of DL-kavain on the mutagenicity and carcinogenicity induced by doxorubicin in Drosophila melanogaster
Journal of Toxicology and Environmental Health, Part A ( IF 2.3 ) Pub Date : 2021-06-27 , DOI: 10.1080/15287394.2021.1942354
Thaís Teixeira da Silva 1, 2 , Júlia Braga Martins 2 , Maria Do Socorro de Brito Lopes 2 , Pedro Marcos de Almeida 2, 3 , José Luiz Silva Sá 1 , Francielle Alline Martins 1, 2
Affiliation  

ABSTRACT

Kavain, kavalactone, present in Piper methysticum exhibits anticonvulsive, analgesic, anxiolytic, antiepileptic, antithrombotic, anti-inflammatory and antioxidant properties. Given its importance, the aim of the present study was to assess (1) the mutagenic and carcinogenicity of kavain administered alone and (2) the antimutagenic and anticarcinogenic potential when administered simultaneously with the chemotherapeutic drug doxorubicin (DXR) using the Somatic Mutation and Recombination Test (SMART) and Epithelial Tumor Test (ETT) using Drosophila melanogaster as a model system. Third-stage larvae from a standard (ST) and high metabolic bioactivation (HB) crosses were treated with different kavain concentrations (32, 64 or 128 μg/ml), alone or in conjunction with DXR (0.125 mg/ml). In ST descendants, kavain produced no significant mutagenic or recombinogenic effects. In the HB cross, mutagenic activity was observed at kavain concentrations of 64 and 128 μg/ml. In the DXR and kavain co-treatment, a modulating effect of the DXR-mediated mutagenic response dependent upon the concentration was detected in both crosses. In ETT, no marked carcinogenic or anticarcinogenic activity was noted for kavain. However, when kavain was combined with DXR synergistic induction of tumors by the chemotherapeutic drug occurred indicating that kavain enhanced the carcinogenic action of DXR.



中文翻译:

DL-kavain对阿霉素致黑腹果蝇致突变性和致癌性的调节作用

摘要

Kavain,卡瓦内酯,存在于Piper methysticum 中,具有抗惊厥、镇痛、抗焦虑、抗癫痫、抗血栓、抗炎和抗氧化特性。鉴于其重要性,本研究的目的是评估 (1) kavain 单独给药的致突变性和致癌性,以及 (2) 使用体细胞突变和重组与化疗药物阿霉素 (DXR) 同时给药时的抗突变和抗癌潜力使用黑腹果蝇进行测试 (SMART) 和上皮肿瘤测试 (ETT)作为模型系统。来自标准 (ST) 和高代谢生物活化 (HB) 杂交的第三阶段幼虫用不同的 kavain 浓度(32、64 或 128 μg/ml)单独或与 DXR(0.125 mg/ml)联合处理。在 ST 后代中,kavain 没有产生显着的致突变或重组效应。在 HB 杂交中,在 64 和 128 μg/ml 的 kavain 浓度下观察到诱变活性。在 DXR 和 kavain 联合处理中,在两个杂交中检测到依赖于浓度的 DXR 介导的诱变反应的调节作用。在 ETT 中,未发现 kavain 有明显的致癌或抗癌活性。然而,当 kavain 与 DXR 结合时,化疗药物会协同诱导肿瘤,这表明 kavain 增强了 DXR 的致癌作用。

更新日期:2021-07-23
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