In Vitro Glucuronidation of Caribbean Ciguatoxins in Fish: First Report of Conjugative Ciguatoxin Metabolites
| Autor: | Lada Ivanova, Jessica Kay Gwinn, Silvio Uhlig, Fedor Kryuchkov, Alison Robertson, Christiane Kruse Fæste |
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| Rok vydání: | 2021 |
| Předmět: |
Food Chain
Ciguatoxin Ciguatera Glucuronidation 010402 general chemistry Toxicology 01 natural sciences Article Ciguatoxins 03 medical and health sciences Glucuronides Biotransformation medicine Animals Humans 14. Life underwater Rats Wistar 030304 developmental biology 0303 health sciences Chemistry Fishes Ciguatera Poisoning General Medicine medicine.disease 0104 chemical sciences Caribbean Region Seafood Biochemistry Bioaccumulation Microsomes Liver Microsome Glucuronide |
| Zdroj: | Chem Res Toxicol |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/acs.chemrestox.1c00181 |
| Popis: | Ciguatoxins (CTX) are potent marine neurotoxins, which can bioaccumulate in seafood, causing a severe and prevalent human illness known as ciguatera poisoning (CP). Despite the worldwide impact of ciguatera, effective disease management is hindered by a lack of knowledge regarding the movement and biotransformation of CTX congeners in marine food webs, particularly in the Caribbean and Western Atlantic. In this study we investigated the hepatic biotransformation of C-CTX across several fish and mammalian species through a series of in vitro metabolism assays focused on phase I (CYP P450; functionalization) and phase II (UGT; conjugation) reactions. Using liquid chromatography high-resolution mass spectrometry to explore potential C-CTX metabolites, we observed two glucuronide products of C-CTX-1/-2 and provided additional evidence from high-resolution tandem mass spectrometry to support their identification. Chemical reduction experiments confirmed that the metabolites were comprised of four distinct glucuronide products with the sugar attached at two separate sites on C-CTX-1/-2 and excluded the C-56 hydroxyl group as the conjugation site. Glucuronidation is a novel biotransformation pathway not yet reported for CTX or other related polyether phycotoxins, yet its occurrence across all fish species tested suggests that it could be a prevalent and important detoxification mechanism in marine organisms. The absence of glucuronidation observed in this study for both rat and human microsomes suggests that alternate biotransformation pathways may be dominant in higher vertebrates. |
| Databáze: | OpenAIRE |
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