prostaglandin, cytokines and angiotensin II are involved. However, the causal mechanisms of the cardiac dysfunction must be well understood in order to develop an appropriate therapy, for severe envenomed cases. The follow up study investigated the relationship between activation of both receptors of angiotensin II type-1 (AT1R) as well as the histamine H4 (H4R), and the severity of the observed cardiac disturbances following envenomation. N.M.R.I mice received a sublethal dose (0.5 mg/kg; sub- cutaneously) of Androctonus Australis hector (Aah) venom with or without AT1R antagonist,valsartan (15 mg /kg/ 15 days; gavage) or an H4R antag- onist, JNJ7777120 (10 mg /kg; subcutaneously). The inflammatory response was evaluated by the assessment of polymorphonuclear leuko- cyte infiltration (neutrophil and eosinophil), into the cardiac tissue. The estimation of some oxidative/nitrosative stress markers (NO, MDA, H2O2, catalase, GSH) was also undertaken, followed by the analysis of the cellular matrix metalloproteinases (MMP-2 and MMP-9) expression. This study was supported by the evaluation of the myocardial tissue alterations and metabolic enzyme activities (CK, LDH) in sera. Results revealed that venom induced a marked infiltration of the immune cells into the myocardium. This was accompanied by increased NO levels, an important lipid peroxi- dation and the alteration of the antioxidant system. Important MMPs expression and severe myocardial alterations, concomitant with elevated enzymatic activities of the metabolic parameters in sera, were also observed. The inhibition of either the AT1 or the H4 receptors before en- venomation resulted in the reduction of the inflammatory cell infiltration and the prevention of the imbalanced redox status. However, the H4 re- ceptor inhibition seemed to be more efficient on the MMps expression in the heart, than the AT1 receptor antagonist. The histopathological analysis revealed the prevention of the myocardial alterations with Valsartan, while the persistence of interstitial edema was still observed, in the presence of JNJ7777120. Furthermore, a marked decrease of the metabolic enzyme activities was recorded following pretreatments. In conclusion, our results suggest the probable contribution of the AT1 and H4 receptors, in the development of induced inflammation in the heart by the venom. Thus, targeting the angiotensin and histaminergic systems would consti- tute a useful tool to better understanding the molecular mechanisms implicated in the envenoming pathogenesis. Keywords: Scorpion envenomation, Inflammation, Cardiac tissue, Angio- tensin II type-1 receptor, Histamine type-4 receptor ASSESSMENT OF SAXITOXIN SENSITIVITY OF NERVES ISOLATED FROM THE PACIFIC OYSTER, CRASSOSTREA GIGAS, EXPOSED TO ALEXANDRIUM MINUTUM Floriane Boullot a , Caroline Fabioux a , H el ene Hegaret a , Philippe Soudant a , Pierre Boudry b , Evelyne Benoit c, * . a Laboratoire des Sciences de l’Environnement Marin (LEMAR), Institut Universitaire Europeen de la Mer, Universite de Bretagne Occidentale, UMR 6539 CNRS/UBO/IRD/Ifremer, 29280, Plouzane, France; b Ifremer (LEMAR), UMR 6539 CNRS/UBO/IRD/ Ifremer, 29280 Plouzane, France; c DRF/iBiTec-S/SIMOPRO, CEA de Saclay, Institut des Neurosciences Paris-Saclay (Neuro-PSI), UMR 9197 CNRS/ Universite Paris-Sud, 91190, Gif-sur-Yvette, France * Corresponding author. E-mail address: evelyne.benoit@cea.fr (E. Benoit). Harmful algal blooms of the genus Alexandrium, producing paralytic shell- fish toxins (PSTs), regularly occur in French coastal waters, contaminating shellfish. Among those, Pacific oysters (Crassostrea gigas) may accumulate high levels of PSTs during these blooms. PSTs are composed of saxitoxin (STX) and analogues which, similarly to tetrodotoxin, block voltage-gated sodium channels and thus inhibit action potentials in excitable cells. The aim of our study was to analyse the PST-sensitivity of C. gigas in relation to toxin bio-accumulation. For this purpose, the STX sensitivity of cerebrovisceral nerves isolated from both field and cultured oysters obtained from a shell- fish farmer, experimentally exposed to A. minutum, was evaluated using an electrophysiological approach. Meanwhile, the PST content of their digestive gland was determined using biochemical analyses. The compound nerve action potential (CNAP) of oysters collected in the field on April 2014 was about 5 fold more sensitive to STX than those collected on October 2015, suggesting that summer exposure to PST-pro- ducing A. minutum bloom potentially resulted in a decreased sensitivity to STX. Additionally, the STX-sensitivity of CNAPs recorded from cultured oysters experimentally fed with A. minutum (toxic-exposed oysters) or Isochrysis sp., a non-toxic micro-algae, (control oysters) revealed that these oysters could be separated into two groups, “resistant” and relatively “sensitive”, independently of their diet. Moreover, the percentage of toxin- “sensitive” nerves was lower and the STX concentration necessary to block 50% of their CNAP was higher in toxic-exposed than control oysters. This supports the above proposed hypothesis stating that toxic-exposed oysters are relatively more resistant to STX than non-exposed ones. However, no obvious correlation was observed between nerve sensitivity to STX and the PST content of oyster digestive gland. In conclusion, C. gigas oyster nerves are shown, for the first time, to have micromolar range of STX sensitivity, which decreases when oysters are exposed to dinoflagellates producing PSTs. Keywords: Crassostrea gigas, Compound nerve action potential, Alexan- drium minutum, Paralytic shellfish toxins MAMBALGINS, SNAKE PEPTIDES AGAINST INFLAMMATORY AND NEUROPATHIC PAIN THROUGH INHIBITION OF ASIC CHANNELS Anne Baron a, b , Sylvie Diochot a, b, * , Miguel Salinas a,b , Abdelkrim Alloui c , Dominique Douguet a , Gilles Mourier d , Pascal Kessler d , Enrico A. Stura d , Thomas Besson a, b , Val erie Friend a, b , Denis Servent d , Alain Eschalier c , Eric Lingueglia a, b . a UniversiteC^ ote d’Azur, CNRS, Institut de Pharmacologie Moleculaire et Cellulaire, Valbonne, France; b LabEx Ion Channel Science and Therapeutics, Valbonne, France; c Universite d'Auvergne, Inserm, NEURO-DOL, Clermont Ferrand, France; d Commissariat  a l'Energie Atomique, iBiTecS, Gif-sur-Yvette, France * Corresponding author. E-mail address: diochot@ipmc.cnrs.fr (S. Diochot). Mambalgins are 57-amino acid peptides isolated from mamba venom. They produce potent analgesic effects in mice against inflammatory pain upon central intrathecal (i.t.), and peripheral local (i.pl.) injections, through inhibition of different ASICs subtypes and involvement of opioid- independent pathways. They produce fewer side effects than morphine and no apparent toxicity. We now show that mambalgins also have an opioid-independent effect on both thermal and mechanical pain upon systemic intravenous (i.v.) admin- istration and are effective against neuropathic pain by i.v., i.t. and i.pl. in- jections. By combining the use of knockdown and knockout animals, we show the critical involvement of peripheral ASIC1b-containing channels in the i.v. effects of mambalgins against inflammatory pain. The potent analgesic effect on neuropathic pain involves two different mechanisms depending on the route of administration, a naloxone-insensitive and ASIC1a-independent ef- fect associated with i.v. injection, and an ASIC1a-dependent and partially naloxone-sensitive effect associated with i.t. injection. We have done in collaboration with the CEA iBiTecS Institute in Gif-sur- Yvette, the full stepwise solid-phase peptide synthesis of mambalgin-1, solved its 3D crystal structure, mapped the pharmacophore, and identified the binding site and the inhibitory mechanism on ASIC1a channels. These findings identify new roles for ASICs in pain pathways, and mam- balgins as new potential analgesics against inflammatory and chronic neuropathic pain. Keywords: ASIC channels, Pain, Mambalgin THERAPEUTIC POTENTIAL OF RATTLESNAKE PLA2: IMPACT IN CYSTIC FIBROSIS Grazyna Faure a, * , Pierre-Jean Corringer a , Aleksander Edelman b . a Institut Pasteur, UniteRecepteurs-Canaux, CNRS, UMR 3571, 25, rue du Dr. Roux, F- 75015, Paris, France; b INSERM U1151, team Canalopathie epitheliales: la mucoviscidose et autres maladies, Universite Paris Descartes, Paris, France * Corresponding author. E-mail address: grazyna.faure-kuzminska@pasteur.fr (G. Faure). Cystic Fibrosis (CF) is a lethal, genetic disease, caused by mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene. CFTR gene encodes a transmembrane protein CFTR, which regulates fluid transport. The most Abstracts / Toxicon 149 (2018) 86e97 93