%0 Journal Article %9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES %A Braidy, N. %A Matin, A. %A Rossi, F. %A Chinain, M. %A Laurent, Dominique %A Guillemin, G. J. %T Neuroprotective effects of rosmarinic acid on ciguatoxin in primary human neurons %D 2014 %L fdi:010061478 %G ENG %J Neurotoxicity Research %@ 1029-8428 %K Ciguatera ; Ciguatoxin ; DNA damage ; NAD(+) ; Neurotoxicity ; Rosmarinic acid %M ISI:000329326900008 %N 2 %P 226-234 %R 10.1007/s12640-013-9429-9 %U https://www.documentation.ird.fr/hor/fdi:010061478 %> https://www.documentation.ird.fr/intranet/publi/2014/02/010061478.pdf %V 25 %W Horizon (IRD) %X 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. %$ 076 ; 020 ; 050