Orsolin P C, Silva-Oliveira R G, Nepomuceno J C
Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, Bloco 2E, Campus Umuarama, Uberlândia, Minas Gerais, Brazil.
Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, Bloco 2E, Campus Umuarama, Uberlândia, Minas Gerais, Brazil; Laboratório de Citogenética e Mutagênese, Centro Universitário de Patos de Minas, Patos de Minas, Minas Gerais, Brazil.
Food Chem Toxicol. 2015 Jul;81:111-119. doi: 10.1016/j.fct.2015.04.004. Epub 2015 Apr 3.
The competitive inhibitors of HMG-CoA reductase, popularly known as statins, exert pleiotropic effects, which result from the ability of statins to inhibit the synthesis of isoprenoids, which are fundamental for the functioning of proteins responsible for intracellular signaling. Some recent studies suggest an important role associated with the use of antineoplastic atorvastatin and rosuvastatin, the statins most widely used today. In this study, the Drosophila wing spot test was used to evaluate possible protective effects of atorvastatin and rosuvastatin against damage induced by DXR. Larvae were chronically treated with negative control (ethanol 5%), positive control (DXR 0.125 mg/mL) and five different concentrations of atorvastatin and rosuvastatin. The results demonstrated absence of a mutagenic effect for the two statins tested. The analysis of the descendants co-treated with DXR and atorvastatin/rosuvastatin revealed a modulatory effect of these statins on damage induced by DXR. This effect was verified in all concentrations tested in the descendants of the ST and HB crosses treated with rosuvastatin, and only in descendants of the HB cross treated with atorvastatin. Induction of apoptosis and antioxidant activity appear to be the main mechanisms involved in reducing the frequency of mutant spots and consequent modulation of the damage induced by DXR.
HMG-CoA还原酶的竞争性抑制剂，即广为人知的他汀类药物，具有多效性，这是由于他汀类药物能够抑制类异戊二烯的合成，而类异戊二烯对于负责细胞内信号传导的蛋白质的功能至关重要。最近的一些研究表明，目前使用最广泛的他汀类药物——抗肿瘤药物阿托伐他汀和瑞舒伐他汀具有重要作用。在本研究中，采用果蝇翅斑试验来评估阿托伐他汀和瑞舒伐他汀对柔红霉素诱导的损伤可能具有的保护作用。用阴性对照（5%乙醇）、阳性对照（0.125mg/mL柔红霉素）以及五种不同浓度的阿托伐他汀和瑞舒伐他汀对幼虫进行长期处理。结果表明，所测试的两种他汀类药物均无诱变作用。对与柔红霉素和阿托伐他汀/瑞舒伐他汀共同处理的后代进行分析发现，这些他汀类药物对柔红霉素诱导的损伤具有调节作用。在用瑞舒伐他汀处理的ST和HB杂交后代所测试的所有浓度中均验证了这种作用，而在用阿托伐他汀处理的后代中，仅在HB杂交后代中验证了这种作用。诱导细胞凋亡和抗氧化活性似乎是降低突变斑频率以及随之调节柔红霉素诱导的损伤的主要机制。
