Neurotoxicity Research

, Volume 25, Issue 2, pp 226–234 | Cite as

Neuroprotective Effects of Rosmarinic Acid on Ciguatoxin in Primary Human Neurons

  • N. Braidy
  • A. Matin
  • F. Rossi
  • M. Chinain
  • D. Laurent
  • G. J. Guillemin
Original Article


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.


Ciguatera 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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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • N. Braidy
    • 1
  • A. Matin
    • 2
  • F. Rossi
    • 3
    • 4
    • 5
    • 6
  • M. Chinain
    • 7
  • D. Laurent
    • 3
    • 4
  • G. J. Guillemin
    • 8
  1. 1.Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of MedicineUniversity of New South WalesSydneyAustralia
  2. 2.Department of Pharmacology, School of Medical Sciences, Faculty of MedicineUniversity of NSWSydneyAustralia
  3. 3.Université de Toulouse, UPS, UMR-152 (Pharma-Dev)Toulouse Cedex 9France
  4. 4.Institut de Recherche pour le Développement (IRD), UMR-152PapeeteFrench Polynesia
  5. 5.Pacific Biotech SASArueFrench Polynesia
  6. 6.Ecosystèmes Insulaires Océaniens, UMR-241Université de la Polynésie françaiseFaa’aFrench Polynesia
  7. 7.Ecosystèmes Insulaires Océaniens, UMR-241, Laboratoire de Recherche sur les Microalgues ToxiquesInstitut Louis MalardéPapeeteFrench Polynesia
  8. 8.Neuroinflammation group, MND and Neurodegenerative Diseases Research Centre, Australian School of Advanced MedicineMacquarie UniversityNorth RydeAustralia

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