|Author(s)||Ruiz Nicolas1, Petit Karina1, Vansteelandt Marieke1, Kerzaon Isabelle1, Baudet Joseph1, Amzil Zouher2, Biard Jean-Francois1, Grovel Olivier1, Pouchus Yves Francois1|
|Affiliation(s)||1 : Univ Nantes, Fac Pharm, MMS, EA 2160, F-44000 Nantes, France.
2 : IFREMER, Phycotoxins Lab, F-44000 Nantes, France.
|Source||Toxicon (0041-0101) (Elsevier), 2010-04 , Vol. 55 , N. 4 , P. 805-810|
|WOS© Times Cited||17|
|Keyword(s)||Domoic acid, Peptaibol, Synergism, Neurotoxicity, Marine-derived fungal metabolite, Diptera larvae bioassay|
|Abstract||Peptaibols are small linear fungal peptides which are produced in the marine environment. They exhibit neurotoxicity by forming pores in neuronal membranes. This work describes their combine effect with domoic acid, a neurotoxic phycotoxin, on Diptera larvae. The Acute toxicity bioassay on this biological model was tested with a panel of different toxins (microbial, algal or fungal). It allowed the discrimination of neurotoxins and non-neurotoxic toxins, and an evaluation of the toxicity level (MED and ED50) which were correlated with published LD50 in mice for neurotoxins tested. The highest activities on this test were found for Na+ channel blockers tetrodotoxin (ED50 = 0.026 mg/kg) and saxitoxin (ED50 = 0.18 mg/kg). Domoic acid was less active with an ED50 = 7.6 mg/kg. For synergism study, longibrachin-A-I, a 20-mer peptaibol isolated from cultures of a marine-derived strain of Trichoderma longibrachiatum Rifai was chosen. Bioassay results confirmed its neuroactivity. Its level of toxicity (ED50 = 270 mg/kg) was lower than those of phycotoxins tested but higher than mycotoxin ones. Injected together, longibrachin-A-I and domoic acid exhibited an increase of their activities. With doses of longibrachin-A-I below its Minimal Effective Dose (MED), the synergism factor which expresses the enhancement of domoic acid toxicity could reach 34.5. Both domoic acid and longibrachin-A-I are acting on ion channels and pores in neuronal membranes which contribute to the intake of Ca2+ into cells.|
Ruiz Nicolas, Petit Karina, Vansteelandt Marieke, Kerzaon Isabelle, Baudet Joseph, Amzil Zouher, Biard Jean-Francois, Grovel Olivier, Pouchus Yves Francois (2010). Enhancement of domoic acid neurotoxicity on Diptera larvae bioassay by marine fungal metabolites. Toxicon, 55(4), 805-810. Publisher's official version : https://doi.org/10.1016/j.toxicon.2009.11.015 , Open Access version : https://archimer.ifremer.fr/doc/00002/11279/