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首页> 外文期刊>Journal of biochemical and molecular toxicology >Differences in susceptibility of HT-29 and A549 cells to statin-induced toxicity: An investigation using high content screening
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Differences in susceptibility of HT-29 and A549 cells to statin-induced toxicity: An investigation using high content screening

机译：HT-29和A549细胞易感性对他汀类药物诱导的毒性的差异：使用高含量筛选进行调查

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摘要

Statins are a group of hydroxymethylglutaryl coenzyme A reductase inhibitors that are used in the treatment of cardiovascular diseases. However, statins have been found to be cytotoxic, and many unexpected side effects have been reported in clinical applications. The susceptibilities of different cell lines toward statins are diverse, and the mechanisms of cytotoxicity remain unknown. Therefore, the present study aimed to investigate differences in the susceptibility to and mechanisms of statin-induced cytotoxicity in two cell lines, HT-29 and A549, using a high content screening-based multiparametric toxicity assay panel. We found that the two cell types exhibited differing susceptibilities to the cytotoxic effects of the different statins. Additionally, the cytotoxicity was inconsistent between different statins in the two cell lines. Four statins with strong cytotoxicity decreased the viability of HT-29 cells via the mitochondrial pathway, as evidenced by decreased mitochon-drial membrane potential, and elevated mitochondrial mass, calcium release and cell apoptosis, and reactive oxygen species. In contrast, these four statins only induced a decrease in the mitochondrial membrane potential in A549 cells. The above results provide an objective reason for future evaluations of cytotoxic differences in cell types and the underlying mechanisms of cytotoxicity in different statins, and provide a good scientific basis for further research on countermeasures against statin-induced cell injuries.
机译：他汀类药物是一组羟甲基戊二酰辅酶a还原酶抑制剂，用于治疗心血管疾病。然而，人们发现他汀类药物具有细胞毒性，临床应用中也出现了许多意想不到的副作用。不同细胞系对他汀类药物的敏感性不同，细胞毒性机制尚不清楚。因此，本研究旨在使用基于高含量筛选的多参数毒性试验小组，研究两种细胞系HT-29和A549对他汀类药物诱导的细胞毒性的易感性和机制的差异。我们发现这两种细胞对不同他汀类药物的细胞毒性作用表现出不同的敏感性。此外，两种细胞系中不同他汀类药物的细胞毒性不一致。四种具有强细胞毒性的他汀类药物通过线粒体途径降低了HT-29细胞的活力，表现为线粒体膜电位降低，线粒体质量、钙释放和细胞凋亡以及活性氧物种升高。相比之下，这四种他汀类药物仅诱导A549细胞线粒体膜电位降低。上述结果为今后评价不同他汀类药物细胞毒性差异及其潜在机制提供了客观依据，并为进一步研究他汀类药物诱导的细胞损伤对策提供了良好的科学依据。

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