Orsolin P C, Silva-Oliveira R G, Nepomuceno J C
Universidade Federal de Uberlândia, Instituto de Genética e Bioquímica, Bloco 2E, Campus Umuarama, Uberlândia, Minas Gerais, Brazil.
Universidade Federal de Uberlândia, Instituto de Genética e Bioquímica, Bloco 2E, Campus Umuarama, Uberlândia, Minas Gerais, Brazil; Centro Universitário de Patos de Minas, Laboratório de Citogenética e Mutagênese, Patos de Minas, Minas Gerais, Brazil.
Food Chem Toxicol. 2016 Apr;90:10-7. doi: 10.1016/j.fct.2016.01.022. Epub 2016 Jan 29.
Simvastatin is an antilipemic drug that promotes inhibition of HMG-CoA reductase. Simvastatin can also inhibit the formation of other products, such as isoprenoids, conferring additional benefits to this drug, which include antiproliferative, anti-invasive and pro-apoptotic effects. This study was carried out with the aim of evaluating the mutagenic/recombinogenic effect of simvastatin as well as the possible modulatory effects of this statin on the DNA damage induced by doxorubicin (DXR). This analysis was performed using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. To study these effects, larvae descendants of both crosses (ST and HB) were chronically treated with five concentrations of simvastatin, separately and in association with DXR. The results revealed no mutagenic/recombinogenic effect of simvastatin for any of the concentrations tested. A modulating effect of simvastatin was also observed on DNA damage induced by DXR. The reduction of total mutant frequency was observed for spots from descendants of both crosses, but the inhibition was more effective in descendants from the standard cross (ST). It is believed that this modulating effect is mainly associated with the antioxidant activity of this class of drugs, although this parameter has not been directly assessed in this study.
辛伐他汀是一种降脂药物，可促进对HMG-CoA还原酶的抑制作用。辛伐他汀还能抑制其他产物的形成，如类异戊二烯，赋予该药物额外的益处，包括抗增殖、抗侵袭和促凋亡作用。本研究旨在评估辛伐他汀的致突变/重组作用，以及该他汀类药物对阿霉素（DXR）诱导的DNA损伤可能的调节作用。该分析使用果蝇的体细胞突变和重组试验（SMART）进行。为研究这些作用，对两个杂交组合（ST和HB）的幼虫后代分别用五种浓度的辛伐他汀进行慢性处理，单独处理以及与DXR联合处理。结果显示，在所测试的任何浓度下，辛伐他汀均无致突变/重组作用。还观察到辛伐他汀对DXR诱导的DNA损伤有调节作用。在两个杂交组合后代的斑点中均观察到总突变频率降低，但在标准杂交组合（ST）的后代中抑制作用更有效。据信，这种调节作用主要与这类药物的抗氧化活性有关，尽管本研究未直接评估该参数。
