The lethal activity of PLlv and BLlv was compared in mice subjected to intradermal toxin injection. We observed that both venoms are lethal to mice, but PLlv was more efficacious than BLlv (LD50 = 1.21 mg/kg and 2.18 mg/kg, respectively). In previous similar studies, with whole venom of five Brazilian Loxosceles species, it was shown that the LD50 of Loxosceles similis was the most lethal in mice (LD50 = 0.32 mg/kg ( Silvestre et al., 2005)); followed PLX-4720 in vivo by LD50 for L. intermedia (0.48 mg/kg ( Barbaro et al., 1996) and 0.5 mg/kg ( Braz et al., 1999), respectively). Different LD50 values were found for L. gaucho venom (0.74 mg/kg ( Barbaro
et al., 1996) and 0.574 mg/kg ( Pretel et al., 2005), respectively); in L. laeta AZD9291 solubility dmso the venom LD50 was 1.45 mg/kg ( Barbaro et al., 1996) and for Loxosceles adelaida venom 0.696 mg/kg ( Pretel et al., 2005). The LD50 for BLlv obtained here is 1.5-fold higher than that obtained by Barbaro et al. (1996). This divergence can be explained because in our experiments venom was collected by extraction after gland dissection as described by da Silveira et al. (2002),whilst
in their study the venom was obtained by electrical stimulation. In addition, interspecies variations in Loxosceles venom composition have been reported ( de Oliveira et al., 2005). The standard murine lethal assay (LD50 of venom and ED50 for antivenom), is viewed as yardstick to determine the neutralizing potency of antivenoms for therapeutic use, and is currently the most accepted method in various countries ( Theakston and Reid, 1983). In Peru, this is the pre-clinical test for assessing the antivenom potency
of anti-loxoscelic antivenom. Since the main effect of Loxosceles envenomation is the development of skin lesions on experimental or fortuitous inoculation ( da Silva et al., 2004), we studied the ability of PLlv to induce dermonecrosis, hemorrhage and edema in rabbits using 10 μg of crude venom. The rationale for this dose of Loxosceles venom is that we determined that this value represents a Minimum Necrotizing Dose (MND)/kg in rabbits when L. intermedia venom (considered as reference venom) Phosphoprotein phosphatase is injected ( Felicori et al., 2006). The results ( Fig. 1) showed that PLlv was capable to produce, 72 h after injection, dermonecrosis, hemorrhage and edema effects with typical pattern development of loxoscelic lesions. Comparative analysis of PLlv and BLlv showed that both Peruvian and Brazilian venoms exhibited same dermonecrotic activities (PLlv and BLlv = 0.53 cm2, approximately). Rabbits injected with PLlv and BLlv showed hemorrhagic area of 3.12 cm2 and 2.85 cm2, respectively. Concerning the edematogenic activity, the rabbits injected with PLlv showed an edematogenic area smaller than the rabbits injected with BLlv (PLlv = 0.845 cm2 and BLlv = 1.04 cm2).