Enhancement of domoic acid neurotoxicity on Diptera larvae bioassay by marine fungal metabolites.
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 ED(50)) which were correlated with published LD(50) in mice for neurotoxins tested. The highest activities on this test were found for Na(+) channel blockers tetrodotoxin (ED(50) = 0.026 mg/kg) and saxitoxin (ED(50) = 0.18 mg/kg). Domoic acid was less active with an ED(50) = 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 (ED(50) = 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 Ca(2+) into cells.
Ruiz
Nicolas
N
University of Nantes, Faculty of Pharmacy, MMS - EA 2160, F-44000 Nantes, France.
Petit
Karina
K
Vansteelandt
Marieke
M
Kerzaon
Isabelle
I
Baudet
Joseph
J
Amzil
Zouher
Z
Biard
Jean-François
JF
Grovel
Olivier
O
Pouchus
Yves François
YF
D000818:Animals; D001681:Biological Assay; D004175:Diptera / Q000187:drug effects* / Q000254:growth & development; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007814:Larva / Q000187:drug effects*; D007928:Lethal Dose 50; D008386:Marine Biology; D021241:Spectrometry, Mass, Electrospray Ionization; D014242:Trichoderma / Q000737:chemistry*
C012301:domoic acid; D007608:Kainic Acid