Laboratorio de Farmacología, Facultad de Química, Universidad Autónoma de Yucatán, Merida 97069, Yucatan, Mexico.
Grupo de Investigación en Química Analítica y Ambiental, Facultad de Química, Universidad Autónoma de Yucatán, Merida 97069, Yucatan, Mexico.
Molecules. 2020 Dec 16;25(24):5959. doi: 10.3390/molecules25245959.
Many studies describe different pharmacological effects of flavonoids on experimental animals and humans. Nevertheless, few ones are confirming the safety of these compounds for therapeutic purposes. This study aimed to investigate the preclinical safety of naringenin, naringin, hesperidin, and quercetin by in vivo, in vitro, and in silico approaches. For this, an MTT-based cytotoxicity assay in VERO and MDCK cell lines was performed. In addition, acute toxicity was evaluated on Wistar rats by OECD Guidelines for the Testing of Chemicals (Test No. 423: Acute Oral Toxicity-Class Method). Furthermore, we used the ACD/Tox Suite to predict toxicological parameters such as hERG channel blockade, CYP450 inhibition, and acute toxicity in animals. The results showed that quercetin was slightly more cytotoxic on cell lines (IC of 219.44 ± 7.22 mM and 465.41 ± 7.44 mM, respectively) than the other citroflavonoids. All flavonoids exhibited an LD value > 2000 mg/kg, which classifies them as low-risk substances as OECD guidelines established. Similarly, predicted LD was LD > 300 to 2000 mg/kg for all flavonoids as acute toxicity assay estimated. Data suggests that all these flavonoids did not show significant toxicological effects, and they were classified as low-risk, useful substances for drug development.
许多研究描述了类黄酮对实验动物和人类的不同药理作用。然而，很少有研究证实这些化合物在治疗用途上的安全性。本研究旨在通过体内、体外和计算方法研究柚皮苷、柚皮苷、橙皮苷和槲皮素的临床前安全性。为此，在 VERO 和 MDCK 细胞系中进行了基于 MTT 的细胞毒性测定。此外，按照经合组织化学品测试指南（测试号 423：急性口服毒性-分类方法），在 Wistar 大鼠中评估了急性毒性。此外，我们使用 ACD/Tox Suite 预测了毒理学参数，如 hERG 通道阻断、CYP450 抑制和动物急性毒性。结果表明，槲皮素对细胞系的细胞毒性略高（IC 分别为 219.44 ± 7.22 mM 和 465.41 ± 7.44 mM），而其他类黄酮的 IC 50 值均>2000 mg/kg，根据经合组织制定的指南，这将它们归类为低风险物质。同样，预测的 LD 值对于所有类黄酮来说均>300 至 2000 mg/kg，这与急性毒性测定估计的 LD 值一致。数据表明，所有这些类黄酮均未显示出明显的毒理作用，且被归类为低风险、对药物开发有用的物质。
