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Betulinic acid modulates urethane-induced genotoxicity and mutagenicity in mice and Drosophila melanogaster.
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2020-02-26 , DOI: 10.1016/j.fct.2020.111228
Victor Constante Oliveira 1 , Maria Paula Carvalho Naves 1 , Cássio Resende de Morais 1 , Sarah Alves Rodrigues Constante 2 , Priscila Capelari Orsolin 2 , Bianca Silva Alves 3 , Francisco Rinaldi Neto 3 , Lucas Henrique Domingos da Silva 3 , Lucas Teixeira Souza de Oliveira 3 , Natália Helen Ferreira 3 , Tábata Rodrigues Esperandim 3 , Wilson Roberto Cunha 3 , Denise Crispim Tavares 3 , Mário Antônio Spanó 1
Affiliation  

Betulinic acid (BA) is a pentacyclic triterpenoid found in several plant species. Urethane (URE) is a known promutagen. Here, we examine the genotoxicity and mutagenicity of BA alone or in combination with URE using the bone marrow micronucleus assay in mice bone marrow cells and the Somatic Mutation and Recombination Test in Drosophila melanogaster. Findings revealed that BA alone was not genotoxic, but reduced the frequency of micronucleus when compared to the positive control. No significant differences were observed in the cytotoxicity. Biochemical analyzes showed no significant differences for liver (AST and ALT) or renal (creatinine and urea) function parameters, indicating the absence of hepatotoxic and nephrotoxic effects. BA alone did not increase the frequency of mutant spots, but reduced the total frequency of mutant spots when co-administered with URE in both ST and HB crosses. In addition, BA reduced the recombinogenic effect of URE at the highest concentrations of both crosses. In conclusion, under experimental conditions, BA has modulatory effects on the genotoxicity induced by URE in mice, as well as in somatic cells of D. melanogaster. We suggest that the modulatory effects of BA may be mainly due to its antioxidant and apoptotic properties.

中文翻译:

桦木酸能调节尿烷在小鼠和果蝇中的遗传毒性和致突变性。

桦木酸(BA)是在几种植物中发现的五环三萜。氨基甲酸酯(URE)是已知的促变原。在这里,我们使用小鼠骨髓细胞中的骨髓微核试验以及果蝇中的体细胞突变和重组试验,对BA单独或与URE联合使用BA的遗传毒性和致突变性进行了研究。研究结果表明,与阳性对照相比,单独使用BA并没有遗传毒性,但减少了微核的发生。在细胞毒性方面未观察到显着差异。生化分析表明,肝(AST和ALT)或肾(肌酐和尿素)功能参数无显着差异,表明没有肝毒性和肾毒性作用。单单BA并没有增加突变点的频率,但在ST和HB杂交中与URE并用时,降低了突变点的总频率。另外,BA在两个杂交的最高浓度下降低了URE的重组产生作用。总之,在实验条件下,BA对由URE引起的小鼠以及黑腹果蝇的体细胞遗传毒性具有调节作用。我们建议BA的调节作用可能主要是由于其抗氧化剂和凋亡特性。
更新日期:2020-02-26
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