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Ichthyotoxic brominated diphenyl ethers from a mixed assemblage of a red alga and cyanobacterium: structure clarification and biological properties.

ABSTRACT: Primary fractions from the extract of a tropical red alga mixed with filamentous cyanobacteria, collected from Papua New Guinea, were active in a neurotoxicity assay. Bioassay-guided isolation led to two natural products (1,2) with relatively potent calcium ion influx properties. The more prevalent of the neurotoxic compounds (1) was characterized by extensive NMR, mass spectrometry, and X-ray crystallography, and shown to be identical to a polybrominated diphenyl ether metabolite present in the literature, but reported with different NMR properties. To clarify this anomalous result, we synthesized a candidate isomeric polybrominated diphenyl ether (3), but this clearly had different NMR shifts than the reported compound. We conclude that the original isolate of 3,4,5-tribromo-2-(2,4-dibromophenoxy)phenol was contaminated with a minor compound, giving rise to the observed anomalous NMR shifts. The second and less abundant natural product (2) isolated in this study was a more highly brominated species. All three compounds showed a low micromolar ability to increase intracellular calcium ion concentrations in mouse neocortical neurons as well as toxicity to zebrafish. Because polybrominated diphenyl ethers have both natural as well as anthropomorphic origins, and accumulate in marine organisms at higher trophic level (mammals, fish, birds), these neurotoxic properties are of environmental significance and concern.

SUBMITTER: Suyama TL

PROVIDER: S-EPMC2813928 | biostudies-literature | 2010 Feb-Mar

REPOSITORIES: biostudies-literature

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Ichthyotoxic brominated diphenyl ethers from a mixed assemblage of a red alga and cyanobacterium: structure clarification and biological properties.

Suyama Takashi L TL Cao Zhengyu Z Murray Thomas F TF Gerwick William H WH

Toxicon : official journal of the International Society on Toxinology 20090726 2-3

Primary fractions from the extract of a tropical red alga mixed with filamentous cyanobacteria, collected from Papua New Guinea, were active in a neurotoxicity assay. Bioassay-guided isolation led to two natural products (1,2) with relatively potent calcium ion influx properties. The more prevalent of the neurotoxic compounds (1) was characterized by extensive NMR, mass spectrometry, and X-ray crystallography, and shown to be identical to a polybrominated diphenyl ether metabolite present in the ...[more]

PMID: 19638282

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Project description:Background/objectivePolybrominated diphenyl ethers (PBDEs) and their hydroxylated (OH-) or methoxylated forms have been detected in humans. Because this raises concern about adverse effects on the developing brain, we reviewed the scientific literature on these mechanisms.Data synthesisMany rodent studies reported behavioral changes after developmental, neonatal, or adult exposure to PBDEs, and other studies documented subtle structural and functional alterations in brains of PBDE-exposed animals. Functional effects have been observed on synaptic plasticity and the glutamate-nitric oxide-cyclic guanosine monophosphate pathway. In the brain, changes have been observed in the expression of genes and proteins involved in synapse and axon formation, neuronal morphology, cell migration, synaptic plasticity, ion channels, and vesicular neurotransmitter release. Cellular and molecular mechanisms include effects on neuronal viability  (via apoptosis and oxidative stress), neuronal differentiation and migration, neurotransmitter release/uptake, neurotransmitter receptors and ion channels, calcium (Ca²⁺) homeostasis, and intracellular signaling pathways.DiscussionBioactivation of PBDEs by hydroxylation has been observed for several endocrine end points. This has also been observed for mechanisms related to neurodevelopment, including binding to thyroid hormone receptors and transport proteins, disruption of Ca²⁺ homeostasis, and modulation of GABA and nicotinic acetylcholine receptor function.ConclusionsThe increased hazard for developmental neurotoxicity by hydroxylated (OH-)PBDEs compared with their parent congeners via direct neurotoxicity and thyroid disruption clearly warrants further investigation into a) the role of oxidative metabolism in producing active metabolites of PBDEs and their impact on brain development; b) concentrations of parent and OH-PBDEs in the brain; and c) interactions between different environmental contaminants during exposure to mixtures, which may increase neurotoxicity.

Dataset Information

Ichthyotoxic brominated diphenyl ethers from a mixed assemblage of a red alga and cyanobacterium: structure clarification and biological properties.

Publications

Ichthyotoxic brominated diphenyl ethers from a mixed assemblage of a red alga and cyanobacterium: structure clarification and biological properties.

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