Ability of fucoidan to prevent muscle necrosis induced by snake venom myotoxins: comparison of high- and low-molecular weight fractions
Fecha
2008
Tipo
artículo original
Autores
Azofeifa Chinchilla, Karol
Angulo Ugalde, Yamileth
Lomonte, Bruno
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Resumen
Fucoidan, a natural polysaccharide extracted from brown seaweed, inhibits the myotoxic phospholipases A2 present in
the venoms of crotalid snakes. This study evaluated the influence of molecular weight on the ability of fucoidan to prevent
muscle necrosis when rapidly administered after injection of a purified myotoxin or crude venom of Bothrops asper, in a
mouse model. It was hypothesized that smaller fucoidan fragments, being of higher diffusibility to tissues, might have a
better neutralizing efficiency in vivo. Fucoidan was subjected to acid hydrolysis to obtain low-molecular weight fragments
(FL), or to gel filtration to isolate its high-molecular weight fraction (FH). These two preparations were standardized to the
same neutralizing potency by preincubation assays, and subsequently tested in vivo, by independent administration assays.
Local i.m. administration of either FH or FL, immediately after i.m. injection of myotoxin II, prevented nearly 50% of
muscle necrosis, albeit with no difference between the two preparations. Muscle necrosis was not reduced when either FH
or FL was administered by i.v. route, immediately after i.m. toxin injection. When tested against crude venom, which
contains several myotoxin isoforms, the immediate in situ i.m. injection of FH still inhibited myonecrosis by nearly one-half
of the effect recorded in the untreated group, whereas FL was ineffective. It is concluded that, in this model, and in contrast
to expectations, the use of smaller fucoidan fragments to prevent muscle damage induced by snake venom myotoxins is not
advantageous, when compared with larger fucoidan molecules.
Descripción
Palabras clave
Myonecrosis, Myotoxin, Fucoidan, Phospholipase A2, Snake venom