Preclinical toxicological assessment of polydatin in zebrafish model

Abstract

Polydatin (3,4’,5-trihydroxystilbene-3-β-D-glucoside, piceid), a natural stilbenoid found in different plant sources, has gained increasing attention for its potential health benefits. However, prior to its widespread adoption in human therapeutics and consumer products, a comprehensive investigation of its toxicological effects is crucial. In this study, the toxicity of polydatin was investigated in a developmental toxicity test using zebrafish (Danio rerio) as a valuable model for preclinical assessments. We employed the Fish Embryo Test (FET test – OECD n°236) to investigate the effects of polydatin on survival, hatchability, development, and behavior of zebrafish embryo-larval stage. Remarkably, the results demonstrated that polydatin up to 435 μM showed no toxicity. Throughout the exposure period, zebrafish embryos exposed to polydatin exhibited normal development, with no significant mortality observed. Furthermore, hatching success and heartbeat rate were unaffected, and no morphological abnormalities were identified, signifying a lack of teratogenic effects and cardiotoxicity. Locomotion activity assessment revealed normal swimming patterns and response to stimuli, indicating no neurotoxic effects. Our study provides valuable insights into the toxicological profile of polydatin, suggesting that it may offer potential therapeutic benefits under a considerable concentration range. In addition, zebrafish model proves to be an efficient system for early-stage toxicological screening, guiding further investigations into the secure utilization of polydatin for human health and wellness.

Graphical Abstract

Keywords:

• Piceid
• resveratrol
• danio rerio
• fish embryo toxicity
• behavior

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, [M.A.H], upon reasonable request.

Additional information

Funding

This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES), under the Capes-PrInt Program [001]; and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [423028/2018–9]. M.A.H. is a productivity fellow of CNPq [309840/2022–8].