Phospholipases A2 isolated from Micrurus lemniscatus coral snake venom: behavioral, electroencephalographic, and neuropathological aspects.
The present study evaluated four phospholipase A2 (PLA2) (Mlx-8, Mlx-9, Mlx-11 and Mlx-12) isolated from Micrurus lemniscatus snake venom (Elapidae). The effects of intrahippocampal administration of these toxins have been determined on behavior, electroencephalography, and neuronal degeneration in rats. These four PLA2 toxins induced motor and EEG alterations in a dose-dependent manner. Behavioral convulsions were characterized by clonic movements and were often accompanied by EEG alterations. Mlx toxins were convulsive but weakly epileptogenic, since low rates of seizure discharges were observed in EEG records. Neuronal injury seemed to depend on the dose of the toxin used. The highest doses of toxins caused severe intoxication and death of some animals. The injury of hippocampal cells was characterized by massive neuronal loss and hippocampal gliosis. A high occurrence of compulsive scratching was observed. Moreover, the onset of seizures induced by Mlx toxins was markedly delayed. The similarities between the effects of Mlx PLA2s and those isolated from other Elapidae snakes venoms suggest that their toxicity are probably due to their specific binding to neuronal membranes and to the catalysis of phospholipid hydrolysis, producing lysophospholipids and fatty acids. These compounds likely disturb the membrane conformation, causing a marked increase in the release of neurotransmitters and concurrent inhibition of vesicle fission and recycling. These toxins can be a useful tool to investigate properties of endogenous secretory PLA2s and therefore may be important both to study mechanisms involved in neurotransmitter release at nerve terminals and to explain the convulsive properties of PLA2s toxins.
Oliveira
D A
DA
Laboratory of Pharmacology, Butantan Institute, Av. Dr. Vital Brasil 1500, São Paulo, Brazil.
Harasawa
C
C
Seibert
C S
CS
Casais e Silva
L L
LL
Pimenta
D C
DC
Lebrun
I
I
Sandoval
M R L
MR
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000737:chemistry* / Q000145:classification; D004569:Electroencephalography / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology; D054467:Phospholipases A2 / Q000032:analysis* / Q000494:pharmacology*; D051381:Rats
D004546:Elapid Venoms; C053972:micrurus venom; D054467:Phospholipases A2