Trintinaglia Michele, de Souza Ana Paula, Gonçalves Trindade Maria Eduarda, Lehmann Mauricio, Conter Felipe Umpierre, Dihl Rafael Rodrigues
Postgraduate Program in Molecular and Cellular Biology Applied to Health, Lutheran University of Brazil (ULBRA), Canoas, Brazil.
J Toxicol Environ Health A. 2025;88(17):688-699. doi: 10.1080/15287394.2025.2491556. Epub 2025 Apr 17.
Myricetin (ME) is a major constituent of various foods and beverages consumed by humans, including vegetables, teas and fruits, and is primarily recognized for its iron-chelating, antioxidant, anti-inflammatory and anti-cancer properties. This study evaluated the cytostatic, genotoxic, and chemopreventive effects of ME in CHO-K1 cells using the Cytokinesis-Block Micronucleus (CBMN) assay and explored molecular interactions through systems biology analysis. CHO-K1 cells were exposed to ME (2.5-40 µM). Cytostasis was assessed by the Cytokinesis-Block Proliferation Index (CBPI), and chromosomal instability was measured by the frequency of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs). ME at 40 µM significantly reduced CBPI, while concentrations of 20 and 40 µM increased chromosomal instability ( < 0.05). For chemoprevention, ME (2.5-10 µM) was administered in pre-, co-, and post-treatment with bleomycin (BLM). ME significantly reduced BLM-induced MNi and NPBs in all protocols ( < 0.05). analysis revealed strong interactions between ME and key proteins related to DNA damage response, apoptosis, and bleomycin detoxification. Notably, the analysis revealed a strong association between ME and bleomycin hydrolase (BLMH) and the interaction of ME with proteins related to DNA damage response and apoptosis regulation. Overall, ME exhibited genotoxicity at high concentrations but demonstrated a significant chemopreventive effect at lower, nontoxic doses. These findings provide insights into the dual biological activity of ME and support its potential use as a protective agent against genotoxic damage.
杨梅素(ME)是人类食用的各种食物和饮料中的主要成分,包括蔬菜、茶和水果,主要因其铁螯合、抗氧化、抗炎和抗癌特性而闻名。本研究使用胞质分裂阻滞微核(CBMN)试验评估了ME对CHO-K1细胞的细胞生长抑制、遗传毒性和化学预防作用,并通过系统生物学分析探索了分子相互作用。将CHO-K1细胞暴露于ME(2.5-40μM)。通过胞质分裂阻滞增殖指数(CBPI)评估细胞生长抑制,通过微核(MNi)、核质桥(NPB)和核芽(NBUD)的频率测量染色体不稳定性。40μM的ME显著降低了CBPI,而20和40μM的浓度增加了染色体不稳定性(P<0.05)。为了进行化学预防,在博来霉素(BLM)的预处理、共处理和后处理中给予ME(2.5-10μM)。在所有方案中,ME均显著降低了BLM诱导的MNi和NPB(P<0.05)。网络分析揭示了ME与DNA损伤反应、细胞凋亡和博来霉素解毒相关的关键蛋白之间的强烈相互作用。值得注意的是,网络分析揭示了ME与博来霉素水解酶(BLMH)之间的强关联以及ME与DNA损伤反应和细胞凋亡调节相关蛋白的相互作用。总体而言,ME在高浓度下表现出遗传毒性,但在较低的无毒剂量下表现出显著的化学预防作用。这些发现为ME的双重生物学活性提供了见解,并支持其作为抗遗传毒性损伤保护剂的潜在用途。