Neuroprotective Effects of Rosmarinic Acid on Ciguatoxin in Primary Human Neurons

作者：Braidy N; Matin A; Rossi F; Chinain M; Laurent D; Guillemin G J^*

来源：Neurotoxicity Research, 2014, 25(2): 226-234.

DOI：10.1007/s12640-013-9429-9

• Ciguatera
• Ciguatoxin
• DNA damage
• NAD(+)
• Neurotoxicity
• Rosmarinic acid

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.

• 出版日期2014-2