PDF(Pubmed)
Abstract：
Hydrogen peroxide is considered deleterious molecule that cause cellular damage integrity and function. Its key redox signaling molecule in oxidative stress and exerts toxicity on a wide range of organisms. Thus, to understand whether oxidative stress alters visual development, zebrafish embryos were exposed to H2O2 at concentration of 0.02 to 62.5 mM for 7 days. Eye to body length ratio (EBR) and apoptosis in retina at 48 hpf, and optomotor response (OMR) at 7 dpf were all measured. To investigate whether hydrogen peroxide-induced effects were mediated by oxidative stress, embryos were co-incubated with the antioxidant, glutathione (GSH) at 50 μM. Results revealed that concentrations of H2O2 at or above 0.1 mM induced developmental toxicity, leading to increased mortality and hatching delay. Furthermore, exposure to 0.1 mM H2O2 decreased EBR at 48 hpf and impaired OMR visual behavior at 7 dpf. Additionally, exposure increased the area of apoptotic cells in the retina at 48 hpf. The addition of GSH reversed the effects of H2O2, suggesting the involvement of oxidative stress. H2O2 decreased the expression of eye development-related genes, pax6α and pax6β. The expression of apoptosis-related genes, tp53, casp3 and bax, significantly increased, while bcl2α expression decreased. Antioxidant-related genes sod1, cat and gpx1a showed decreased expression. Expression levels of estrogen receptors (ERs) (esr1, esr2α, and esr2β) and ovarian and brain aromatase genes (cyp19a1a and cyp19a1b, respectively) were also significantly reduced. Interestingly, co-incubation of GSH effectivity reversed the impact of H2O2 on most parameters. Overall, these results demonstrate that H2O2 induces adverse effects on visual development via oxidative stress, which leads to alter apoptosis, diminished antioxidant defenses and reduced estrogen production.
摘要：
过氧化氢被认为是导致细胞损伤完整性和功能的有害分子。其在氧化应激中的关键氧化还原信号分子，并对广泛的生物体产生毒性。因此，为了了解氧化应激是否会改变视觉发育，将斑马鱼胚胎暴露于浓度为0.02至62.5mM的H2O2中7天。48hpf时视网膜的眼长比（EBR）和细胞凋亡，和在7dpf时的视运动反应(OMR)都被测量。为了研究过氧化氢诱导的作用是否由氧化应激介导，胚胎与抗氧化剂共同孵育，谷胱甘肽(GSH)为50μM。结果表明，浓度为0.1mM或以上的H2O2诱导发育毒性，导致死亡率增加和孵化延迟。此外，暴露于0.1mMH2O2可在48hpf时降低EBR，在7dpf时损害OMR视觉行为。此外,暴露在48hpf时增加了视网膜中凋亡细胞的面积。GSH的添加逆转了H2O2的作用，表明参与了氧化应激。H2O2降低了眼部发育相关基因的表达，pax6α和pax6β。凋亡相关基因的表达，tp53，casp3和bax，显著增加,而bcl2α表达降低。抗氧化相关基因sod1、cat和gpx1a表达降低。雌激素受体（ERs）的表达水平（esr1，esr2α，和esr2β）以及卵巢和脑芳香化酶基因（cyp19a1a和cyp19a1b，分别)也显著减少。有趣的是,GSH有效性的共孵育逆转了H2O2对大多数参数的影响。总的来说,这些结果表明，H2O2通过氧化应激对视觉发育产生不利影响，导致细胞凋亡改变，减少抗氧化剂防御和减少雌激素的产生。
