Zhang Ji-Liang, Laurence Souders Christopher, Denslow Nancy D, Martyniuk Christopher J
Henan Open Laboratory of Key Subjects of Environmental and Animal Products Safety, College of Animal Science and Technology, Henan University of Science and Technology, Henan, China; Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, UF Genetics Institute, University of Florida, Gainesville, FL 32611, USA.
Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, UF Genetics Institute, University of Florida, Gainesville, FL 32611, USA.
Toxicol Appl Pharmacol. 2017 Jul 15;327:30-38. doi: 10.1016/j.taap.2017.04.024. Epub 2017 Apr 25.
Quercetin is a natural product that is sold as a supplement in health food stores. While there are reported benefits for this flavonoid as a dietary supplement due to antioxidant properties, the full scope of its biological interactions has not been fully addressed. To learn more about the mechanisms of action related to quercetin, we exposed zebrafish (Danio rerio) embryos to 1 and 10μg/L quercetin for 96h starting at 3h post fertilization. Quercetin up to 10μg/L did not induce significant mortality in developing fish, but did increase prevalence of an upward-curved dorsal plane in hatched larvae. To determine whether this developmental defect was potentially related to mitochondrial bioenergetics during development, we measured oxygen consumption rate in whole embryos following a 24-hour exposure to quercetin. Basal mitochondrial and ATP-linked respiration were decreased at 1 and 10μg/L quercetin, and maximal respiration was decreased at 10μg/L quercetin, suggesting that quercetin impairs mitochondrial bioenergetics. This is proposed to be related to the deformities observed during development. Due to the fact that ATP production was affected by quercetin, larval behaviors related to locomotion were investigated, as well as transcriptional responses of six myogenesis transcripts. Quercetin at 10μg/L significantly reduced the swimming velocity of zebrafish larvae. The expression levels of both myostatin A (mstna) and myogenic differentiation (myoD) were also altered by quercetin. Mstna, an inhibitory factor for myogenesis, was significantly increased at 1μg/L quercetin exposure, while myoD, a stimulatory factor for myogenesis, was significantly increased at 10μg/L quercetin exposure. There were no changes in transcripts related to apoptosis (bcl2, bax, casp3, casp7), but we did observe a decrease in mRNA levels for catalase (cat) in fish exposed to each dose, supporting an oxidative stress response. Our data support the hypothesis that quercetin may affect locomotion and induce deformities in zebrafish larvae by diminishing ATP production and by altering the expression of transcripts related to muscle formation and activity.
槲皮素是一种天然产物，在健康食品商店作为补充剂出售。虽然据报道这种类黄酮作为膳食补充剂具有抗氧化特性的益处，但其生物相互作用的全貌尚未得到充分研究。为了更多地了解与槲皮素相关的作用机制，我们从受精后3小时开始，将斑马鱼（Danio rerio）胚胎暴露于1和10μg/L的槲皮素中96小时。高达10μg/L的槲皮素不会在发育中的鱼类中诱导显著死亡率，但确实会增加孵化幼虫中背侧平面向上弯曲的发生率。为了确定这种发育缺陷是否可能与发育过程中的线粒体生物能量学有关，我们在暴露于槲皮素24小时后测量了整个胚胎的耗氧率。在1和10μg/L槲皮素处理下，基础线粒体呼吸和ATP相关呼吸均降低，在10μg/L槲皮素处理下最大呼吸降低，表明槲皮素损害线粒体生物能量学。这被认为与发育过程中观察到的畸形有关。由于ATP产生受槲皮素影响，因此研究了与运动相关的幼虫行为以及六种肌生成转录本的转录反应。10μg/L的槲皮素显著降低了斑马鱼幼虫的游泳速度。槲皮素还改变了肌肉生长抑制素A（mstna）和成肌分化（myoD）的表达水平。mstna是一种肌生成抑制因子，在暴露于1μg/L槲皮素时显著增加，而myoD是一种肌生成刺激因子，在暴露于10μg/L槲皮素时显著增加。与凋亡相关的转录本（bcl2、bax、casp3、casp7）没有变化，但我们确实观察到暴露于每种剂量的鱼类中过氧化氢酶（cat）的mRNA水平降低，支持氧化应激反应。我们的数据支持这样的假设，即槲皮素可能通过减少ATP产生以及改变与肌肉形成和活动相关的转录本表达来影响斑马鱼幼虫的运动并诱导畸形。
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