Pharmacological modulation of edema induced by Lys-49 and Asp-49 myotoxic phospholipases A2 isolated from the venom of the snake Bothrops asper (terciopelo)
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Abstract
The pharmacological modulation of edema-forming activity of Bothrops asper myotoxins
II and III, Lys-49 and Asp-49 phospholipases A2, respectively, was studied plethysmographically
in the mouse foot pad model. Myotoxin III had phospholipase A2 activity, whereas myotoxin
II was devoid of enzymatic activity when tested on egg yolk phosphatidylcholine. Both
toxins induced a dose-dependent edema of rapid onset. Chemical modification of myotoxin
III with p-bromophenacyl bromide abrogated enzymatic activity and significantly reduced
edemat-forming activity, although a residual effect remained. Pre-treatment of animals
with diphenhydramine, dexamethasone, indomethacin and prazosin significantly reduced
the effect of both myotoxins. It is concluded that (a) these myotoxins are important
edema-forming components of B. asper venom, (b) enzymatic activity is not a strict
requirement to exert this effect, although in the case of myotoxin III it contributes
to its development, and (c) several inflammatory mediators participate in mouse foot
pad edema induced by these myotoxins.