PHARMACOLOGICAL MODULATION OF EDEMA INDUCED BY LYS-49 AND ASP-49 MYOTOXIC PHOSPHOLIPASES A(2) ISOLATED FROM THE VENOM OF THE SNAKE BOTHROPS-ASPER (TERCIOPELO)

The pharmacological modulation of edema-forming activity of Bothrops a sper myotoxins II and III, Lys-49 and Asp-49 phospholipases A(2), resp ectively, was studied plethysmographically in the mouse foot pad model . Myotoxin III had phospholipase A(2) activity, whereas myotoxin II wa s devoid of enzymatic activity when tested on egg yolk phosphatidylcho line. Both toxins induced a dose-dependent edema of rapid onset. Chemi cal modification of myotoxin III with p-bromophenacyl bromide abrogate d enzymatic activity and significantly reduced edema-forming activity, although a residual effect remained. Pretreatment of animals with dip henhydramine, dexamethasone, indomethacin and prazosin significantly r educed the effect of both myotoxins. It is concluded that (a) these my otoxins are important edema-forming components of B. asper venom, (b) enzymatic activity is not a strict requirement to exert this effect, a lthough 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. (C) 1998 Elsevier Science Ltd. All r ights reserved.