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双酚 A 对视网膜色素上皮细胞的细胞遗传毒性受含瓜拉那、硒和左旋肉碱的多种补充剂的差异调节。

Bisphenol-A induced cyto-genotoxicity on retinal pigment epithelial cells is differentially modulated by a multi-supplement containing guarana, selenium, and L-carnitine.

机构信息

Universidade Federal de Santa Maria - UFSM, Centro de Ciências da Saúde, Departamento de Morfologia, Programa de Pós-graduação em Farmacologia, Laboratório de Biogenômica, Santa Maria, RS, Brasil.

Universidade Federal de Santa Maria - UFSM, Centro de Ciências da Saúde, Departamento de Morfologia, Laboratório de Biogenômica, Santa Maria, RS, Brasil.

出版信息

Braz J Biol. 2024 Jul 5;84:e282840. doi: 10.1590/1519-6984.282840. eCollection 2024.

DOI:10.1590/1519-6984.282840
PMID:38985071
Abstract

Bisphenol A (BPA) may adversely affect human health by inducing oxidative stress and irreversible damage to cells. Bioactive compounds found in some functional foods, individually or in combination, can attenuate the negative effects of BPA exposure; an example is the multi-supplement containing guarana (Gua), selenium (Se), and L-carnitine (LC) -GSC- which has already demonstrated antioxidant, genoprotective, and immunomodulatory activities. This study aimed to determine the effect of GSC and its constituents on oxidative and genotoxic alterations triggered by BPA exposure in the retinal epithelial cell line. The cells exposed to BPA (0.001, 0.01, 0.1, 1, 3, and 10 µM) to determine the lowest concentration required to induce cyto-genotoxicity. ARPE-19 cells were then concomitantly exposed to the selected BPA concentration, GSC, and its components (Gua, 1.07 mg/mL; Se, 0.178 µg/mL; and LC, 1.43 mg/mL). Flow cytometry, biochemical assays, qRT-PCR, genotoxicity, apoptosis, and cellular proliferation. Based on our results, 10 µM of BPA could induce cyto-genotoxic and oxidative alterations. BPA did not alter the Bcl-2/BAX expression ratio but induced Casp3 and Casp8 overexpression, suggesting that apoptosis was induced mainly via the extrinsic pathway. GSC partially reversed the alterations triggered by BPA in ARPE-19 cells. However, Se had unexpected negative effects on ARPE-19 cells. The multi-supplement GSC may attenuate changes in oxidative and genotoxic markers related to exposure of ARPE-19 cells to BPA. our results revealed that the antioxidant, anti-apoptotic, and genoprotective properties of GSC were not universally shared by its individual, once Se did not exhibit any positive impact.

摘要

双酚 A (BPA) 可能通过诱导氧化应激和细胞不可逆损伤对人类健康产生不利影响。一些功能性食品中发现的生物活性化合物,单独或联合使用,可减轻 BPA 暴露的负面影响;例如,含有瓜拉那 (Gua)、硒 (Se) 和左旋肉碱 (LC) 的多补充剂 -GSC- 已经显示出抗氧化、基因保护和免疫调节活性。本研究旨在确定 GSC 及其成分对 BPA 暴露在视网膜上皮细胞系中引起的氧化和遗传毒性改变的影响。将细胞暴露于 BPA(0.001、0.01、0.1、1、3 和 10 µM),以确定诱导细胞遗传毒性所需的最低浓度。然后,将 ARPE-19 细胞同时暴露于选定的 BPA 浓度、GSC 及其成分(瓜拉那 1.07mg/mL;硒 0.178µg/mL;左旋肉碱 1.43mg/mL)。流式细胞术、生化分析、qRT-PCR、遗传毒性、细胞凋亡和细胞增殖。根据我们的结果,10µM 的 BPA 可诱导细胞遗传毒性和氧化改变。BPA 并未改变 Bcl-2/BAX 表达比率,但诱导 Casp3 和 Casp8 过表达,表明细胞凋亡主要通过外在途径诱导。GSC 部分逆转了 BPA 对 ARPE-19 细胞引发的改变。然而,Se 对 ARPE-19 细胞产生了意想不到的负面影响。多补充剂 GSC 可能减轻 ARPE-19 细胞暴露于 BPA 时与氧化和遗传毒性标记物相关的变化。我们的结果表明,GSC 的抗氧化、抗凋亡和基因保护特性并非其单个成分所共有,因为 Se 并未表现出任何积极影响。

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