Fucoidan, a natural
polysaccharide extracted from brown seaweed, inhibits the myotoxic
phospholipases A(2) 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 (F(L)), or to gel filtration to isolate its high-molecular weight fraction (F(H)). 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 F(H) or F(L), 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 F(H) or F(L) 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 F(H) still inhibited myonecrosis by nearly one-half of the effect recorded in the untreated group, whereas F(L) 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.