Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro- Institute for Innovation, Capacity Building and Sustainability of Agri-food Production. University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; Institute for Research and Innovation in Health (i3s), Laboratory Animal Science (LAS), Institute of Molecular and Cell Biology (IBMC), University of Porto (UP), Porto, Portugal.
Life Sciences and Environment School (ECVA), University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.
Comp Biochem Physiol C Toxicol Pharmacol. 2021 Nov;249:109143. doi: 10.1016/j.cbpc.2021.109143. Epub 2021 Jul 18.
Previous embryonic fish data have shown caffeine to induce potential teratogenic and long-term neurodevelopmental outcomes through oxidative stress-mediated apoptosis. In this context, antioxidants may have the potential to counteract the caffeine-induced effects. Therefore, the present study aimed to investigate the potential protective role of 24-epibrassinolide (24-EPI), a natural brassinosteroid with proven antioxidant properties, against caffeine-induced teratogenic effects during early zebrafish development. Embryos (~2 h post-fertilization - hpf) were exposed to 0.5 mM caffeine, co-exposed to 24-EPI (0.01, 0.1 and 1 μM) and to 24-EPI alone (1 μM) for 96 h. During exposure, lethal and sublethal developmental parameters were evaluated. At the end of the exposure, biochemical evaluations were made, and 24 h after, different behavioural paradigms were assessed. An increased number of animals showing oedema and malformations were observed after caffeine exposure, while these were reduced after co-exposure to 24-EPI concentration, namely the tail curvature. The results showed oxidative stress and related parameters similar among treatments. Yet, caffeine exposure resulted in locomotor deficits (decreased speed and distance) and disrupted anxiety-like and avoidance responses. The co-exposure to caffeine and to the highest 24-EPI concentrations resulted in less pronounced behavioural deficits. Overall, there was an absence of effects in the embryo/larvae exposed solely to 24-EPI, while caffeine caused developmental and neurotoxic effects. Although further studies are needed, the results showed promising protective effects of the highest 24-EPI concentration tested against the toxicity induced by caffeine in zebrafish.
先前的胚胎鱼类数据表明，咖啡因通过氧化应激介导的细胞凋亡诱导潜在的致畸和长期神经发育后果。在这种情况下，抗氧化剂可能具有抵消咖啡因诱导作用的潜力。因此，本研究旨在探讨 24-表油菜素内酯（24-EPI）的潜在保护作用，24-EPI 是一种具有抗氧化特性的天然油菜素内酯，可抵抗咖啡因在早期斑马鱼发育过程中引起的致畸作用。胚胎（受精后约 2 小时-2 hpf）暴露于 0.5 mM 咖啡因中，同时暴露于 24-EPI（0.01、0.1 和 1 μM）和单独的 24-EPI（1 μM）中 96 小时。在暴露期间，评估了致死和亚致死发育参数。暴露结束时进行生化评估，暴露后 24 小时评估不同的行为范式。与咖啡因单独暴露相比，观察到更多的动物出现水肿和畸形，而与 24-EPI 共暴露时，这些动物的数量减少，例如尾弯曲。结果表明，在不同处理组之间氧化应激和相关参数相似。然而，咖啡因暴露导致运动缺陷（速度和距离降低）以及焦虑样和回避反应受损。与咖啡因共暴露于最高浓度的 24-EPI 导致不那么明显的行为缺陷。总的来说，仅暴露于 24-EPI 的胚胎/幼鱼没有出现影响，而咖啡因则引起了发育和神经毒性作用。尽管还需要进一步的研究，但结果表明，在斑马鱼中，最高浓度的 24-EPI 对咖啡因诱导的毒性具有有希望的保护作用。
