Student Research Committee, Health Research Center, Babol University of Medical Sciences, Babol, Iran.
Department of Pharmacology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran.
Toxicol Mech Methods. 2023 Nov;33(6):502-511. doi: 10.1080/15376516.2023.2188928. Epub 2023 Mar 13.
5-fluorouracil (5-FU) is a widely used chemotherapeutic agent, and its uncontrolled blood levels contribute to toxicity. Quercetin, as an important flavonoid, has many biological effects, including anti-tumor and anti-inflammatory features. The current study investigated the synergistic effect between 5-FU and quercetin using HT-29 cell line and fibroblast cells. Rats were assigned to two groups. The 5-FU/quercetin group received intraperitoneal quercetin (10 mg/kg) and the Tween was injected to the control group for 14 consecutive days. On the 15th day, both groups received 50 mg/kg of 5-FU. Upon the final injection, blood samples were obtained at different times. Pharmacokinetic parameters were evaluated using high-performance liquid chromatography (HPLC). The mean (±SD) of maximum plasma concentration (C) of 5-FU in combination therapy group was 3.10 ± 0.18 μg/ml and the area under the curve (AUC) was 153.89 ± 21.36, which increased by 113% and 128% compared to control group, respectively. Quercetin increased anti-tumor activity of 5-FU and enhanced C and AUC of 5-FU. These findings confirm the synergistic effects between quercetin and 5-FU at the usual doses in cancer treatment, which may lead to reduced toxicity.
5-氟尿嘧啶（5-FU）是一种广泛使用的化疗药物，其不受控制的血液水平会导致毒性。槲皮素作为一种重要的类黄酮，具有许多生物学效应，包括抗肿瘤和抗炎特性。本研究使用 HT-29 细胞系和成纤维细胞研究了 5-FU 和槲皮素之间的协同作用。大鼠分为两组。5-FU/槲皮素组腹腔注射槲皮素（10mg/kg），对照组注射吐温 14 天。第 15 天，两组均给予 50mg/kg 的 5-FU。最后一次注射后，在不同时间采集血样。采用高效液相色谱法（HPLC）评估药代动力学参数。联合治疗组 5-FU 的最大血浆浓度（C）的平均值（±SD）为 3.10±0.18μg/ml，曲线下面积（AUC）为 153.89±21.36，分别比对照组增加了 113%和 128%。槲皮素增加了 5-FU 的抗肿瘤活性，并增强了 5-FU 的 C 和 AUC。这些发现证实了槲皮素和 5-FU 在癌症治疗中的常规剂量下具有协同作用，这可能会降低毒性。
