24-Epibrassinolide modulates the neurodevelopmental outcomes of high caffeine exposure in zebrafish (Danio rerio) embryos

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology 2021-11, Vol.249, p.109143, Article 109143
• Main Authors: Félix, Luís, Lobato-Freitas, Carolina, Monteiro, Sandra M., Venâncio, Carlos
• Format: Article
• Language: English
• Subjects: Abnormalities, Drug-Induced - etiology; Animals; Behavior, Animal - drug effects; Brassinosteroid; Brassinosteroids - pharmacology; Caffeine; Caffeine - administration & dosage; Caffeine - toxicity; Developmental abnormalities; Embryo, Nonmammalian - drug effects; Embryonic Development - drug effects; Female; Larva - drug effects; Locomotor activity; Male; Oxidative stress; Steroids, Heterocyclic - pharmacology; Teratogens - toxicity; Toxicity Tests - methods; Zebrafish - abnormalities; Zebrafish - embryology; Zebrafish embryo
• ISSN: 1532-0456; 1878-1659
• DOI: 10.1016/j.cbpc.2021.109143

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. [Display omitted] •Zebrafish embryos were exposed to caffeine, 24-EPI and co-exposed to caffeine and 24-EPI for 96 h.•Exposure to caffeine increased the mortality rate which was ameliorated by 1 μM 24-EPI.•Caffeine and 24-EPI co-exposure resulted in no biochemical changes.•Caffeine induced behaviour deficits while 24-EPI restored behavioural functions.•Disruption of anxiety-like behaviours was induced by caffeine but alleviated by 24-EPI.