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An approach to evaluating the potential teratogenic and neurotoxic mechanism of BHA based on apoptosis induced by oxidative stress in zebrafish embryo (Danio rerio).
Human & Experimental Toxicology ( IF 2.8 ) Pub Date : 2020-09-10 , DOI: 10.1177/0960327120952140
A Baran 1 , S Yildirim 2 , A Ghosigharehaghaji 3 , İ Bolat 2 , E Sulukan 3 , S B Ceyhun 3, 4
Affiliation  

Butylated hydroxyanisole (BHA) has been widely used in the cosmetics, pharmaceutical, and food industries due to its antioxidant activity. Despite the antioxidant effects, reported adverse effects of BHA at the cellular level have made its use controversial. In this regard, this study was performed to elucidate the potential toxicity mechanism caused by BHA at the molecular level in zebrafish embryos. For this purpose, zebrafish embryos were exposed to BHA at levels of 0.5, 1, 5, 7.5 and 10 ppm and monitored at 24, 48, 72 and 96 hours. Survival rate, hatching rate and malformations were evaluated. We examined the potential for reactive oxygen species (ROS) production and apoptosis signalling accumulation in the whole body. Moreover, we evaluated histopathological and immunohistochemical (8-OHDG) characterization of the brain in zebrafish embryos at the 96th hour. We also examined apoptosis, histopathological and immunohistochemical (8-OHDG) characteristics in 96 hpf zebrafish larvae exposed to tertiary butylhydroquinone (TBHQ), one of the major metabolites of BHA, at doses of 0.5, 2.5, 3.75 and 5 ppm. Consequently, it has been considered that increased embryonic and larval malformations in this study may have been caused by ROS-induced apoptosis. After 96 h of exposure, positive 8-OHdG immunofluorescence, degenerative changes, and necrosis were observed in the brain of BHA and TBHQ-treated zebrafish larvae in a dose-dependent manner. BHA and TBHQ exposure could lead to an increase in 8-OHdG activities by resulting oxidative DNA damage. In particular, the obtained data indicate that the induction of ROS formation, occurring during exposure to BHA and/or multiple hydroxyl groups, could be responsible for apoptosis.



中文翻译:

基于斑马鱼胚胎氧化应激诱导的细胞凋亡评估 BHA 潜在的致畸和神经毒性机制的方法 (Danio rerio)。

丁基羟基茴香醚 (BHA) 由于其抗氧化活性而被广泛应用于化妆品、制药和食品行业。尽管具有抗氧化作用,但据报道 BHA 在细胞水平上的不利影响使其使用存在争议。在这方面,本研究旨在从分子水平上阐明斑马鱼胚胎中 BHA 引起的潜在毒性机制。为此,斑马鱼胚胎暴露于 0.5、1、5、7.5 和 10 ppm 的 BHA,并在 24、48、72 和 96 小时进行监测。评估存活率、孵化率和畸形。我们检查了全身活性氧 (ROS) 产生和细胞凋亡信号积累的潜力。而且,我们评估了第 96 小时斑马鱼胚胎大脑的组织病理学和免疫组织化学 (8-OHDG) 表征。我们还检测了暴露于 0.5、2.5、3.75 和 5 ppm 剂量的叔丁基氢醌 (TBHQ)(BHA 的主要代谢物之一)的 96 hpf 斑马鱼幼虫的细胞凋亡、组织病理学和免疫组织化学 (8-OHDG) 特征。因此,本研究中认为胚胎和幼虫畸形增加可能是由 ROS 诱导的细胞凋亡引起的。暴露 96 小时后,在 BHA 和 TBHQ 处理的斑马鱼幼虫的大脑中以剂量依赖性方式观察到 8-OHdG 免疫荧光阳性、退行性变化和坏死。BHA 和 TBHQ 暴露可导致 DNA 氧化损伤,从而导致 8-OHdG 活性增加。特别是,

更新日期:2020-09-10
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