Ranking the cytotoxic potency of Ostreopsis cf. ovata, Ostreopsis cf. siamensis (O. sp. 9), and purified ovatoxins in human keratinocytes

IF 4.1 1区生物学 Q1 MARINE & FRESHWATER BIOLOGY

Harmful Algae Pub Date : 2025-12-01 Epub Date: 2025-10-10 DOI:10.1016/j.hal.2025.103000

Loïc Plessis , Korian Lhaute , Fabienne Hervé , Madeleine Thimann , Véronique Séchet , Liliane Carpentier , Ariana B. Moutinho , Tiago Simões , Ana Amorim , Kevin Henry , Jorge L.B. Neves , Léana Gorse , Margaux Paradis , Stéphanie Brédif , Philipp Hess , Damien Réveillon

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Abstract

Ovatoxins (OVTXs), a family of marine polyketides structurally similar to palytoxin (PLTX), are suspected to cause respiratory symptoms and skin irritation among coastal users during blooms of the dinoflagellate Ostreopsis cf. ovata. To investigate their role in cutaneous toxicity, crude extracts from six O. cf. ovata strains (OVTX(+) and OVTX(−)) and three O. cf. siamensis (O. sp. 9) strains (OVTX(−)), along with six purified OVTX analogs, were tested for cytotoxicity (MTT assay) and cell death phenotypes (microscopy) in human keratinocyte models. Interestingly, cytotoxicity was driven by OVTX content, while OVTX(−) extracts were, on average, 150-fold and >1000-fold less potent for O. cf. siamensis and O. cf. ovata, respectively. Nevertheless, the latter two induced PLTX-like cell death, suggesting the presence of unidentified PLTX-like toxins. Purified OVTXs exhibited sub-nanomolar cytotoxicity, 3.5- to 12.5-fold lower than PLTX (IC₅₀ = 0.036–0.642 nM vs. 0.011–0.049 nM), ranking in potency: PLTX > OVTX-d > OVTX-b > OVTX-a > OVTX-c > OVTX-e >>> OVTX-h (non-toxic, likely due to ring-opening). This study demonstrates the high toxic potency of OVTXs, close to that of PLTX, while providing a comprehensive cytotoxicity assessment of OVTX analogs, which could be useful for assessing the risks of human exposure.

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对Ostreopsis cf. ovata, Ostreopsis cf. siamensis （O. sp. 9）和纯化的卵细胞毒素在人角质形成细胞中的细胞毒性进行排名

卵泡毒素（OVTXs）是一种结构类似于palytoxin （PLTX）的海洋多酮类化合物，在鞭毛藻Ostreopsis cfv . ovata繁殖期间，被怀疑在沿海使用者中引起呼吸道症状和皮肤刺激。为了研究它们在皮肤毒性中的作用，在人角质细胞模型中，对6株O. cf. ovata菌株（OVTX（+）和OVTX(−)）和3株O. cf. siamensis （O. sp. 9）菌株（OVTX(−)）的粗提取物以及6种纯化的OVTX类似物进行了细胞毒性（MTT法）和细胞死亡表型（显微镜）检测。有趣的是，细胞毒性是由OVTX含量驱动的，而OVTX（−）提取物对O. cf. siamensis和O. cf. ovata的毒性分别平均低150倍和1000倍。然而，后两种药物诱导pltx样细胞死亡，表明存在未知的pltx样毒素。纯化的OVTXs具有亚纳米级的细胞毒性，比PLTX低3.5- 12.5倍（IC50 = 0.036-0.642 nM vs. 0.011-0.049 nM），效价顺序为：PLTX >； OVTX-d > OVTX-b > OVTX-a > OVTX-c > OVTX-e >>> > OVTX-h（无毒，可能是由于环打开）。本研究证明了OVTX的高毒性效力，接近PLTX，同时提供了OVTX类似物的全面细胞毒性评估，这可能有助于评估人类暴露的风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Harmful Algae 生物-海洋与淡水生物学

CiteScore

12.50

自引率

15.20%

发文量

122

审稿时长

7.5 months

期刊介绍： This journal provides a forum to promote knowledge of harmful microalgae and macroalgae, including cyanobacteria, as well as monitoring, management and control of these organisms.