The present study aimed to evaluate the viability of the sponge implant model in mice, considering the need of further investigation of the GKT137831 purchase body’s reaction to the venom. In this model, a fibrovascular tissue induced by subcutaneous implantation of a synthetic matrix mimics the events of cutaneous wound healing (inflammatory infiltrate cells, angiogenesis, fibrogenesis) as assessed by biochemical,

histological, cellular and functional parameters ( Marques et al., 2011, Campos et al., 2011 and Andrade and Ferreira, 2009). Indeed, using this model we have previously shown that intra-implant injection of Bothrops jararaca venom resulted in decreased blood flow detected by slow 133Xenom washout ( Vieira et al., 1992). In the present study, it was possible to observe biochemical Raf inhibitor and histological changes induced by intra-implant injection of 0.5 μg of L. similis crude venom. The alterations included an inflammatory infiltrate predominantly neutrophilic at the injection site, vasodilatation, hyperhaemia, and edema, characterizing an acute inflammation. Besides, hemorrhage, and rupture of the vascular wall were also observed. Interestingly, these events are similar to those observed by several authors in rabbit, guinea pig and human but not in mice skin ( Smith and Micks, 1970, Patel et al., 1994, Ospedal et al., 2002, Pereira et al., 2010, Sunderkötter et al., 2001, Ospedal et al., 2002 and Barbaro Cyclooxygenase (COX) et al.,

2010). The difference

in sensitivity between different species to spider venoms has been attributed to many factors (tissue damage, secondary vascular injury, release of inflammatory mediators) and to insufficient membrane lipid components such as sphingomyelin and products ( He et al., 2001 and Domingos et al., 2003). It has been demonstrated that co-administration of Loxosceles gaucho venom with sphingomyelin intradermally in mice caused the development of an inflammatory reaction at the site of injection. This effect has been attributed to the ability of this molecule to trap the venom for a long period preventing its diffusion systemically ( Domingos et al., 2003). It is possible that the pool of molecules in the implant microenvironment was also able to keep the Loxosceles similis venom allowing for its prolonged action in the newly formed fibrovascular tissue. It may be argued that the highly permeable nature of the neovasculature would allow rapid diffusion of the venom. However, the lytic activity of the venom promoting blood vessel wall rupture intraimplant prevented its release from the site of injection. Further investigation will be necessary to identify the nature of the molecules present in implant compartment responsible for keeping the venom and/or its active fraction. The levels of cytokines VEGF (Vascular Endothelial Growth Factor) and TNF-α (Tumor necrosis factor-α) were also evaluated in the present study.