Bisphenol‐A‐glycidyldimethacrylate (BisGMA) is a resin monomer frequently used in dentin restorative treatments. The leakage of BisGMA monomer from BisGMA‐based polymeric resins can lead to cytotoxicity in macrophages. Rutin has various beneficial bioeffects, including antioxidation and antiinflammation. In this study, we found that pretreatment of RAW264.7 macrophages with rutin‐inhibited cytotoxicity induced by BisGMA in a concentration‐dependent manner. BisGMA‐induced apoptosis, which was detected by levels of phosphatidylserine from the internal to the external membrane and formation of sub‐G1, and genotoxicity, which was detected by cytokinesis‐blocked micronucleus and single‐cell gel electrophoresis assays, were inhibited by rutin in a concentration‐dependent manner. Rutin suppressed the BisGMA‐induced activation of caspase‐3 and ‐9 rather than caspase‐8. Rutin inhibited the activation of the mitochondrial apoptotic pathway, including cytochrome C release and mitochondria disruption, after macrophages were treated with BisGMA. Finally, BisGMA‐induced reactive oxygen species (ROS) generation and antioxidant enzyme (AOE) deactivation could be reversed by rutin. Parallel trends were observed in the elevation of AOE activation and inhibition of ROS generation, caspase‐3 activity, mitochondrial apoptotic pathway activation, and genotoxicity. These results suggested that rutin suppressed BisGMA‐induced cytotoxicity through genotoxicity, the mitochondrial apoptotic pathway, and relatively upstream factors, including reduction of ROS generation and induction of AOE.

中文翻译：

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芦丁保护的 BisGMA 通过减少线粒体凋亡途径和诱导抗氧化酶诱导巨噬细胞的细胞毒性、基因毒性和凋亡

双酚-A-二甲基丙烯酸缩水甘油酯（BisGMA）是一种常用于牙本质修复治疗的树脂单体。BisGMA 单体从 BisGMA 基聚合物树脂中的泄漏可能会导致巨噬细胞的细胞毒性。芦丁具有多种有益的生物效应，包括抗氧化和抗炎。在这项研究中，我们发现用芦丁预处理 RAW264.7 巨噬细胞可以以浓度依赖性方式抑制 BisGMA 诱导的细胞毒性。BisGMA 诱导的细胞凋亡（通过从内膜到外膜的磷脂酰丝氨酸水平和亚 G1 的形成来检测）和基因毒性（通过胞质分裂阻断微核和单细胞凝胶电泳检测来检测）在芦丁中被抑制。浓度依赖性方式。芦丁抑制 BisGMA 诱导的 caspase-3 和 ‐9 激活，而不是 caspase-8。用 BisGMA 处理巨噬细胞后，芦丁抑制线粒体凋亡途径的激活，包括细胞色素 C 释放和线粒体破坏。最后，芦丁可以逆转 BisGMA 诱导的活性氧 (ROS) 生成和抗氧化酶 (AOE) 失活。在 AOE 激活的升高和 ROS 生成的抑制、caspase-3 活性、线粒体凋亡途径激活和遗传毒性方面观察到平行趋势。这些结果表明芦丁通过基因毒性、线粒体凋亡途径和相对上游因素（包括减少ROS生成和诱导AOE）抑制BisGMA诱导的细胞毒性。