Szabó Emília Rita, Plangár Imola, Tőkés Tünde, Mán Imola, Polanek Róbert, Kovács Róbert, Fekete Gábor, Szabó Zoltán, Csenki Zsolt, Baska Ferenc, Hideghéty Katalin
1 Attosecond Light Pulse Source, ELI-HU Nonprofit Ltd., Szeged, Hungary .
2 MTA-SE NAP B Cognitive Translational Behavioural Pharmacology Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University , Budapest, Hungary .
Zebrafish. 2016 Dec;13(6):481-488. doi: 10.1089/zeb.2016.1269. Epub 2016 Aug 3.
This work establishes the zebrafish embryo model for ionizing radiation (IR) modifier research and also evaluates the protective effect of l-alpha glycerylphosphorylcholine (GPC). Embryos were exposed to a single-fraction whole-body gamma irradiation (5, 10, 15, and 20 Gy) at different postfertilization time points and were serially assessed for viability and macro- and micromorphologic abnormalities. After toxicity evaluation, 194 μM of GPC was added for certain groups with 3-h incubation before the radiation. Nuclear factor kappa B (NF-κB) and interleukin-1β (IL-1β) expression changes were measured using quantitative real-time polymerase chain reaction. A higher sensitivity could be observed at earlier stages of the embryogenesis. The lethal dose (LD) for 6 hours postfertilization (hpf) embryos was 15 Gy and for 24 hpf was 20 Gy on day 7, respectively. GPC administration resulted in a significant improvement in both the distortion rate and survival of the 24 hpf embryos. Qualitative evaluation of the histological changes confirmed the protective effect of GPC. IL-1β and NF-κB overexpression due to 10 Gy irradiation was also reduced by GPC. GPC exhibited promising radioprotective effects in our zebrafish embryo model, decreasing the irradiation-induced morphological damage and lethality with significant reduction of IR-caused pro-inflammatory activation.
本研究建立了用于电离辐射(IR)修饰剂研究的斑马鱼胚胎模型,并评估了l-α甘油磷酸胆碱(GPC)的保护作用。在不同的受精后时间点,将胚胎暴露于单次全身γ辐射(5、10、15和20 Gy),并对其活力以及宏观和微观形态异常进行连续评估。在毒性评估后,对某些组在辐射前3小时加入194μM的GPC进行孵育。使用定量实时聚合酶链反应测量核因子κB(NF-κB)和白细胞介素-1β(IL-1β)的表达变化。在胚胎发育的早期阶段可以观察到更高的敏感性。受精后6小时(hpf)胚胎的致死剂量(LD)在第7天分别为15 Gy,受精后24 hpf胚胎的致死剂量为20 Gy。给予GPC可显著改善24 hpf胚胎的畸变率和存活率。组织学变化的定性评估证实了GPC的保护作用。GPC还降低了10 Gy辐射引起的IL-1β和NF-κB过表达。在我们的斑马鱼胚胎模型中,GPC表现出有前景的辐射防护作用,减少了辐射诱导的形态损伤和致死率,并显著降低了IR引起的促炎激活。