Neuroprotective Effects of Rosmarinic Acid on Ciguatoxin in Primary Human Neurons
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Ciguatoxin (CTX), is a toxic compound produced by microalgae (dinoflagellate) Gambierdiscus spp., and is bio-accumulated and bio-transformed through the marine food chain causing neurological deficits. To determine the mechanism of CTX-mediated cytotoxicity in human neurons, we measured extracellular lactate dehydrogenase (LDH) activity, intracellular levels of nicotinamide adenine dinucleotide (NAD+) and H2AX phosphorylation at serine 139 as a measure for DNA damage in primary cultures of human neurons treated with Pacific (P)-CTX-1B and P-CTX-3C. We found these marine toxins can induce a time and dose-dependent increase in extracellular LDH activity, with a concomitant decline in intracellular NAD+ levels and increased DNA damage at the concentration range of 5–200 nM. We also showed that pre- and post-treatment with rosmarinic acid (RA), the active constituent of the Heliotropium foertherianum (Boraginaceae) can attenuate CTX-mediated neurotoxicity. These results further highlight the potential of RA in the treatment of CTX-induced neurological deficits.
KeywordsCiguatera Ciguatoxin DNA damage NAD+ Neurotoxicity Rosmarinic acid
Dr Fanny Rossi was supported by a CIFRE grant from the Pacific Biotech company subsidised by the ANRT (No 1005/2010). Financial support was also insured by Tahiti Fa.’ahotu. Dr Nady Braidy is the recipient of the Alzheimer’s Australia Viertel Foundation and the National Health and Medical Research Early Career Postdoctoral Research Fellowship at the University of New South Wales. The National Health and Medical Research Council and the Australian Research Council also supported this research.
Conflict of interest
There is no conflict of interest in the reported work.
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