Palombo Philipp, Bürkle Alexander, Moreno-Villanueva Maria
Molecular Toxicology Group, Department of Biology, Box 628, University of Konstanz, 78457, Konstanz, Germany.
Molecular Toxicology Group, Department of Biology, Box 628, University of Konstanz, 78457, Konstanz, Germany; Human Performance Research Centre, Department of Sport Science, Box 30, University of Konstanz, 78457, Konstanz, Germany.
Chem Biol Interact. 2022 Apr 25;357:109877. doi: 10.1016/j.cbi.2022.109877. Epub 2022 Mar 8.
In vitro mechanistic research is mostly performed without taking into consideration the potential influence of cell culture media and/or their supplements and therefore, interactions between compounds of interest and medium ingredients may be overlooked. Isoproterenol (isoprenaline) is a synthetic catecholamine used as sympathomimetic drug that stimulates β-adrenergic receptors and is widely used in biomedical research. Clinical studies have shown that isoproterenol is rapidly metabolized in the human body with a plasma half-life of about 2-5 min. However, despite its use in many in vitro and ex vivo studies, the stability of isoproterenol in cell culture media has not been characterized. Our results show a decrease of isoproterenol concentration in RPMI medium but high stability of the compound in TexMACS medium. The isoproterenol oxidation product isoprenochrome forms during treatment in both media. However, isoprenochrome formation is significantly lower in TexMACS medium. The effective level of isoproterenol and the formation of oxidation products might explain the discrepancies observed in isoproterenol-induced genotoxicity and cytotoxicity.
体外机制研究大多在未考虑细胞培养基和/或其补充剂潜在影响的情况下进行，因此，目标化合物与培养基成分之间的相互作用可能被忽视。异丙肾上腺素是一种合成儿茶酚胺，用作拟交感神经药物，可刺激β-肾上腺素能受体，广泛应用于生物医学研究。临床研究表明，异丙肾上腺素在人体中迅速代谢，血浆半衰期约为2至5分钟。然而，尽管它在许多体外和离体研究中被使用，但其在细胞培养基中的稳定性尚未得到表征。我们的结果表明，RPMI培养基中异丙肾上腺素浓度降低，但该化合物在TexMACS培养基中具有高稳定性。在两种培养基处理过程中均会形成异丙肾上腺素氧化产物异戊色素。然而，TexMACS培养基中异戊色素的形成明显较低。异丙肾上腺素的有效水平和氧化产物的形成可能解释了在异丙肾上腺素诱导的遗传毒性和细胞毒性中观察到的差异。
