Department of Biochemistry, Faculty of Pharmacy, University of Tuzla, Tuzla, Bosnia and Herzegovina.
SEE Region Department, Bosnalijek d.d., Sarajevo, Bosnia and Herzegovina.
Adv Med Sci. 2023 Sep;68(2):258-264. doi: 10.1016/j.advms.2023.07.002. Epub 2023 Jul 19.
For many years, statins have been the most commonly used drugs in cholesterol-lowering therapy. In addition to these therapeutic effects, statins exhibit other, pleiotropic effects that can be beneficial, but also harmful to cells and tissues. The aim of this research was to determine and compare the pleiotropic effects of structurally different statins: atorvastatin, simvastatin and rosuvastatin at different concentrations on hepatocellular carcinoma (HepG2) cells.
The MTT assay was used to determine the cytotoxic effects of statins. The influence of statins on the production of reactive oxygen species (ROS) was determined by measuring fluorescent response of 2,7-dichlorofluorescein diacetate (DCFH-DA). The effect of statins on glucose production and excretion was determined with glucose production assay.
The obtained results confirmed that all tested statins exhibit cytotoxic effects, increase the production of ROS as well as the production and excretion of glucose from HepG2 cells. It was observed that all the mentioned effects are more pronounced with lipophilic statins, atorvastatin and simvastatin compared to hydrophilic rosuvastatin.
The less pronounced pleiotropic effects of rosuvastatin on HepG2 cells are probably due to differences in structure and solubility compared to atorvastatin and simvastatin. Transporter-dependent and a slower influx of rosuvastatin into cells compared to the tested lipophilic statins probably lead to a weaker accumulation of rosuvastatin in HepG2 cells, which results in less pronounced pleiotropic effects compared to lipophilic atorvastatin and simvastatin.
多年来，他汀类药物一直是降胆固醇治疗中最常用的药物。除了这些治疗作用外，他汀类药物还具有其他的多效作用，这些作用可能有益，也可能对细胞和组织有害。本研究旨在确定和比较结构不同的他汀类药物（阿托伐他汀、辛伐他汀和瑞舒伐他汀）在不同浓度下对肝癌（HepG2）细胞的多效作用。
采用 MTT 法测定他汀类药物的细胞毒性作用。通过测量 2,7-二氯荧光素二乙酸酯（DCFH-DA）的荧光响应来测定他汀类药物对活性氧（ROS）产生的影响。用葡萄糖产生测定法测定他汀类药物对葡萄糖产生和排泄的影响。
研究结果证实，所有测试的他汀类药物均具有细胞毒性作用，增加 ROS 的产生，以及 HepG2 细胞中葡萄糖的产生和排泄。观察到所有这些作用在亲脂性他汀类药物阿托伐他汀和辛伐他汀中比亲水性瑞舒伐他汀更为明显。
瑞舒伐他汀对 HepG2 细胞的多效作用不那么明显，可能是由于其结构和溶解度与阿托伐他汀和辛伐他汀不同所致。与测试的亲脂性他汀类药物相比，瑞舒伐他汀可能依赖转运蛋白且进入细胞的速度较慢，导致瑞舒伐他汀在 HepG2 细胞中的积累较弱，因此与亲脂性阿托伐他汀和辛伐他汀相比，其多效作用不那么明显。
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