Evaluation of relative potency of calibrated ciguatoxin congeners by near-infrared fluorescent receptor binding and neuroblastoma cell-based assays.

Toxicon

Osaka Prefecture University, Department of Biological Science, Graduate School of Science, 1-2 Gakuen-cho, Sakai-shi, Osaka, 599-8570, Japan; Osaka Metropolitan University, Department of Biological Chemistry, Graduate School of Science, 1-2 Gakuen-cho, Sakai-shi, Osaka, 599-8570, Japan. Electronic address:

Published: July 2023

AI Article Synopsis

  • Ciguatera fish poisoning (CFP) affects over 50,000 people globally each year and is caused by consuming fish and invertebrates that have ciguatoxins (CTXs).
  • The study focuses on improving detection methods for CTXs in fish, specifically developing a near-infrared fluorescent ligand in receptor binding assays and a faster neuroblastoma cell-based assay.
  • Results show that while the receptor binding assay had consistent binding affinities across CTX variants, this didn't correlate with their toxicity in mice, whereas the neuroblastoma assay correlated well with toxicity measurements, enhancing the assessment of CTX risks.

Article Abstract

Ciguatera fish poisoning (CFP) is a foodborne illness affecting > 50,000 people worldwide annually. It is caused by eating marine invertebrates and fish that have accumulated ciguatoxins (CTXs). Recently, the risk of CFP to human health, the local economy, and fishery resources have increased; therefore, detection methods are urgently needed. Functional assays for detecting ciguatoxins in fish include receptor binding (RBA) and neuroblastoma cell-based assay (N2a assay), which can detect all CTX congeners. In this study, we made these assays easier to use. For RBA, an assay was developed using a novel near-infrared fluorescent ligand, PREX710-BTX, to save valuable CTXs. In the N2a assay, a 1-day assay was developed with the same detection performance as the conventional 2-day assay. Additionally, in these assays, we used calibrated CTX standards from the Pacific determined by quantitative NMR for the first time to compare the relative potency of congeners, which differed significantly among previous studies. In the RBA, there was almost no difference in the binding affinity among congeners, showing that the differences in side chains, stereochemistry, and backbone structure of CTXs did not affect the binding affinity. However, this result did not correlate with the toxic equivalency factors (TEFs) based on acute toxicity in mice. In contrast, the N2a assay showed a good correlation with TEFs based on acute toxicity in mice, except for CTX3C. These findings, obtained with calibrated toxin standards, provide important insights into evaluating the total toxicity of CTXs using functional assays.

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http://dx.doi.org/10.1016/j.toxicon.2023.107161DOI Listing

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