In vitro and in vivo modulation of inducible nitric oxide synthase gene expression in a mouse model for ciguatera.

Titre: 
In vitro and in vivo modulation of inducible nitric oxide synthase gene expression in a mouse model for ciguatera.
Auteurs: 
Pauillac S, Kumar-Roine S, Matsui M, Reybier K, Darius HT, Chinain M, Laurent D
Type de communication: 
Communication orale
Conférence: 
Congrès Ciguatéra et Biotoxines associées (Nouméa, Nouvelle-Calédonie)
Année: 
10/2008

Ciguatoxins (CTXs), a class of potent lipid-soluble neurotoxins produced by certain strains of the marine dinoflagellate Gambierdiscus spp, are responsible for ciguatera fish poisoning (CFP). Extensive pharmacological studies have previously revealed the mode of action of CTXs on various voltage-gated ion channels (Na+, K+ and Ca2+), but these interactions cannot totally account for the multifaceted nature and the manifestation of certain intense inflammatory symptoms of CFP.
The involvement of the nitric oxide (NO) pathway in CFP has been investigated, in vitro and in vivo, in a (CTX)/mouse model. The modulation of inducible nitric oxide synthase (iNOS) synthesis at the mRNA level was kinetically measured using real-time PCR technology. Murine macrophage cells ( RAW 264.7) treated with P-CTX-1B (the most potent Pacific congener; 6 nM) and peripheral blood mononuclear cells from P-CTX-1B-injected mice (1ng/g), were demonstrated to express iNOS in a time-dependent manner. This strongly suggests that NO might be responsible for certain CFP symptoms (e.g. hypotension, allergenic effects and Chronic Fatigue Syndrome). This hypothesis is further supported by the observation that the most currently used drugs for the treatment of CFP are free radical scavengers. In conclusion, the implication of NO in CFP paves the way for new therapies for both occidental and traditional medicines.

Workshop international Ciguatéra et biotoxines associées (Nouméa, 27-31 octobre 2008)