Short-term exposure of Cannabidiol on Zebrafish (Danio Rerio): Reproductive Toxicity

Lin, Li; Fan, Bei; Kong, Zwe‐Ling; Zhang, Yifan; Zhao, Mengying; Simal-Gándara, Jesús; Wang, Fengzhong; Li, Minmin

doi:10.1007/s11356-023-27792-7

Cited by 4 publications

(1 citation statement)

References 38 publications

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“…Fenfluramine, at concentrations as high as 25 mg/kg, failed to show protection against hyperthermia-induced seizures in Scn1a A1783/WT mice 55 . In contrast, five different synthetic cannabinoids [note: cannabadiol is oil-based and short-term exposure is toxic to zebrafish larvae 56 ] reduced high-velocity seizure-like behaviors and suppressed electrographic seizure activity in scn1lab ( didy s552 ) zebrafish mutants 31 . In addition to highlighting the predictive pharmacological validity of scn1lab zebrafish models these studies also emphasize the importance of incorporating multiple outcome measures e.g., toxicity, behavior and electrophysiology.…”

Section: Discussionmentioning

confidence: 99%

Testing of putative antiseizure drugs in a preclinical Dravet syndrome zebrafish model

Whyte-Fagundes,

Vance,

Carroll

et al. 2023

Preprint

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Dravet syndrome (DS) is a severe genetic epilepsy primarily caused byde novomutations in a voltage-activated sodium channel gene (SCN1A). Patients face life-threatening seizures that are largely resistant to available anti-seizure medications (ASM). Preclinical DS animal models are a valuable tool to identify candidate ASMs for these patients. Among these,scn1labmutant zebrafish exhibiting spontaneous seizure-like activity are particularly amenable to large-scale drug screening. Prior screening in ascn1labmutant zebrafish line generated using N-ethyl-N-nitrosourea (ENU) identified valproate, stiripentol, and fenfluramine e.g., Federal Drug Administration (FDA) approved drugs with clinical application in the DS population. Successful phenotypic screening inscn1labmutant zebrafish consists of two stages: (i) a locomotion-based assay measuring high-velocity convulsive swim behavior and (ii) an electrophysiology-based assay, usingin vivolocal field potential (LFP) recordings, to quantify electrographic seizure-like events. Using this strategy more than 3000 drug candidates have been screened inscn1labzebrafish mutants. Here, we curated a list of nine additional anti-seizure drug candidates recently identified in preclinical models: 1-EBIO, AA43279, chlorzoxazone, donepezil, lisuride, mifepristone, pargyline, soticlestat and vorinostat. First-stage locomotion-based assays inscn1labmutant zebrafish identified only 1-EBIO, chlorzoxazone and lisuride. However, second-stage LFP recording assays did not show significant suppression of spontaneous electrographic seizure activity for any of the nine anti-seizure drug candidates. Surprisingly, soticlestat induced frank electrographic seizure-like discharges in wild-type control zebrafish. Taken together, our results failed to replicate clear anti-seizure efficacy for these drug candidates highlighting a necessity for strict scientific standards in preclinical identification of ASMs.

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Section: Discussionmentioning

confidence: 99%