Can quercetin reduce arsenic induced toxicity in mouse BALB/c 3T3 fibroblast cells? A study involving in vitro, molecular docking, and ADME predictions.

IF 2.8 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Velid Unsal, Cumali Keskin, Erkan Oner
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引用次数: 0

Abstract

This study aimed to investigate the protective effect of quercetin against arsenic-induced oxidative damage, inflammation, and apoptosis in mouse BALB/c 3T3 fibroblast cells (NIH-3T3). Arsenic at different concentrations of 0.05 µM (low), 0.5 µM (medium), 10 µM (high) doses were used to induce toxicity, while 120 μm quercetin was used for treatment. MTT and LDH analyses were performed to determine the effect of arsenic and quercetin on cell viability, while oxidative stress markers and antioxidant enzyme activities were measured by spectrophotometric method. TNF-α and IL-1β levels were measured by the ELISA method, Autodock programs were used for molecular docking studies. In addition, computer-based analyses of quercetin and succimer molecules were performed using SwissADME web tools. TNF-α (PDB ID: 2AZ5), IL-1β (PDB ID: 1ITB), Caspase3 (PDB ID: 2XYG), Bax (PDB ID: 4S0O), SOD (PDB ID:1CBJ), GSH-Px (PDB ID: 1GP1) and Bcl-2 (PDB ID: 1G5M) crystal structures were obtained from the Protein Data Bank. Bax and Bcl-2 levels of apoptotic genes and mRNA expression levels of Caspase-3 activity were measured using the QRT-PCR technique. TUNEL staining was performed to determine DNA fragmentations, while DAPI staining was done to visualise nuclear modifications. Quercetin has been found to significantly reduce oxidative stress, inflammation, and apoptosis in cells and exert anti-apoptotic effects. Molecular docking studies revealed quercetin shows good binding affinity with molecules with SOD, GSH-Px, Bax, Bcl-2, Caspase-3, TNF-α and IL-1β structures, and has been observed to bind with Bax and Bcl-2 with molecular docking scores of -7.5 and - 7.7 kcal/mol, respectively. These findings are supported by results showing that quercetin is effective in anti-apoptotic and anti-inflammatory processes in arsenic-induced cells under in vitro conditions. In addition, when ADME values are examined, it can be considered that quercetin is a useful and effective candidate compound in reducing arsenic toxicity, considering its higher synthetic accessibility score, better pharmacokinetic properties, and good biological transition and interaction capacities compared to succimer.

本研究旨在探讨槲皮素对砷诱导的小鼠BALB/c 3T3成纤维细胞(NIH-3T3)氧化损伤、炎症和细胞凋亡的保护作用。实验采用不同浓度的砷,分别为 0.05 µM(低剂量)、0.5 µM(中等剂量)和 10 µM(高剂量)来诱导毒性,同时使用 120 μm 的槲皮素进行处理。通过 MTT 和 LDH 分析确定砷和槲皮素对细胞活力的影响,同时采用分光光度法测定氧化应激标记物和抗氧化酶活性。采用酶联免疫吸附法测定 TNF-α 和 IL-1β 的水平,并使用 Autodock 程序进行分子对接研究。此外,还使用 SwissADME 网络工具对槲皮素和琥珀酰亚胺分子进行了计算机分析。TNF-α(PDB ID:2AZ5)、IL-1β(PDB ID:1ITB)、Caspase3(PDB ID:2XYG)、Bax(PDB ID:4S0O)、SOD(PDB ID:1CBJ)、GSH-Px(PDB ID:1GP1)和 Bcl-2(PDB ID:1G5M)晶体结构来自蛋白质数据库。采用 QRT-PCR 技术测定凋亡基因 Bax 和 Bcl-2 的水平以及 Caspase-3 活性的 mRNA 表达水平。TUNEL染色用于测定DNA片段,DAPI染色用于观察核修饰。研究发现,槲皮素能显著减少细胞的氧化应激、炎症和凋亡,并具有抗凋亡作用。分子对接研究显示,槲皮素与具有 SOD、GSH-Px、Bax、Bcl-2、Caspase-3、TNF-α 和 IL-1β 结构的分子具有良好的结合亲和力,并观察到槲皮素与 Bax 和 Bcl-2 的分子对接得分分别为 -7.5 和 - 7.7 kcal/mol。研究结果表明,在体外条件下,槲皮素对砷诱导的细胞具有抗凋亡和抗炎作用。此外,在研究 ADME 值时,考虑到槲皮素与琥珀酰亚胺相比具有更高的合成可得性得分、更好的药代动力学特性以及良好的生物转化和相互作用能力,可以认为槲皮素是一种有用且有效的降低砷毒性的候选化合物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Pharmacology & Toxicology
BMC Pharmacology & Toxicology PHARMACOLOGY & PHARMACYTOXICOLOGY&nb-TOXICOLOGY
CiteScore
4.80
自引率
0.00%
发文量
87
审稿时长
12 weeks
期刊介绍: BMC Pharmacology and Toxicology is an open access, peer-reviewed journal that considers articles on all aspects of chemically defined therapeutic and toxic agents. The journal welcomes submissions from all fields of experimental and clinical pharmacology including clinical trials and toxicology.
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