However, the pre-treatment with other anti-inflammatory drugs (H1 receptor antagonist

and non-selective COX inhibitor) had less effect on this response. Unlike the persistent protective effect of aprotinin and icatibant, the latter drugs were efficient in attenuating the edematogenic response only in the first 30 min. These results evidences that one of the main pathways involved in SpV-induced edema is the kallikrein-kinin system (KKS), and suggests that histamine receptors and production of arachidonic acid metabolites are involved in an initial phase of edema generation. The KKS participation also has been demonstrated in edema response induced by Bothrops lanceolatus ( Faria et al., 2001) and Trimeresurus mucrosquamatus ( Wang and Teng, 1988) snake venoms, Lonomia obliqua caterpillar bristles ( Bohrer et al.,

learn more 2007), Vespula vulgaris wasp ( Griesbacher et al., 1998) and the toadfish T. nattereri ( Lopes-Ferreira click here et al., 2004). Investigations upon the molecular mechanisms underlying the inflammatory activity of fish venoms revealed different classes of toxins involved. Inflammation resulting from local administration of T. nattereri venom was related to a new class of kininogenases of 35–40 kDa, named Natterins ( Magalhães et al., 2006). In addition, further inflammatory reaction was associated with a Th1 response induced by a 15 kDa lectin-like protein present in this venom, Nattectin ( Saraiva et al., 2011). Junqueira et al. (2007) suggested that the inflammatory activity provoked by catfish C. spixii venom was also related with 14 kDa proteins. However in stonefish Synanceja horrida venom, which is considered one of the most dangerous fish in the world, the local inflammation was attributed to the action of a multifunctional toxin named Stonustoxin.

Besides its edematogenic activity, this toxin was also lethal, hemolytic and active in vascular preparations ( Low et al., 1993; Poh et al., 1991). A fraction exhibiting similar pharmacological properties was detected in Synanceja trachynis venom ( Kreger, 1991), and further was called Trachynilysin ( Colasante et al., 1996). Both stonefish toxins are ∼150 kDa proteins possessing subunits of 70–85 kDa, and probably its effects result from a non-specific cell membrane disturbing action ( Kreger, Adenosine triphosphate 1991; Chen et al., 1997). Since kallikrein-like enzymes have been extensively described in a large number of animal venoms, and their activity is intrinsically related with venom inflammatory potential, we decided to investigate the presence of such proteases in S. plumieri venom. Despite SpV hydrolyzed specific substrates for kinin-releasing enzymes (containing the signature Pro-Phe-Arg), screening the fractions eluted from gel filtration chromatography ( Fig. 5) revealed that this activity was mainly detected in F1 and mismatched with the edema inducing fractions (F2 and F3).