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Neuroprotective Effects of Rosmarinic Acid on Ciguatoxin in Primary Human Neurons |
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| Authors: | N. Braidy A. Matin F. Rossi M. Chinain D. Laurent G. J. Guillemin |
| Affiliation: | 1. Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia 2. Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, University of NSW, Sydney, NSW, 2052, Australia 3. Université de Toulouse, UPS, UMR-152 (Pharma-Dev), rte de Narbonne, 31062, Toulouse Cedex 9, France 4. Institut de Recherche pour le Développement (IRD), UMR-152, BP 529, 98713, Papeete, Tahiti, French Polynesia 5. Pacific Biotech SAS, BP 140 289, 98701, Arue, Tahiti, French Polynesia 6. Ecosystèmes Insulaires Océaniens, UMR-241, Université de la Polynésie fran?aise, BP 6570, 98702, Faa’a, Tahiti, French Polynesia 7. Ecosystèmes Insulaires Océaniens, UMR-241, Laboratoire de Recherche sur les Microalgues Toxiques, Institut Louis Malardé, BP 30, 98713, Papeete, Tahiti, French Polynesia 8. Neuroinflammation group, MND and Neurodegenerative Diseases Research Centre, Australian School of Advanced Medicine, Macquarie University, North Ryde, NSW, Australia |
| Abstract: | 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. |
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