3). Dynorphin1-13 (dyn A, YGGFLRRIRPKLK) was also hydrolyzed Panobinostat solubility dmso by the crude venom of B. jararaca, showing at least two cleavage points (YGGFLR-RIRPK-LK), since the fragment RIRPK was detected by mass spectrometry analyses. Unlike angiotensin I, dyn A is hydrolyzed by both classes of proteases, metallo- and serine peptidases, so this activity was partially blocked by the commercial antibothropic serum. The pathophysiological mean of dyn A hydrolyzes is possibly correlated with pain sensation and inflammation ( Parikh et al., 2010 and Luo et al., 2008). Many factors,

including phylogeny, sex, geographic origin, season, age and prey preference, Cytoskeletal Signaling inhibitor may influence composition of the venoms (Chippaux et al., 1991, Mackessy et al., 2003 and Furtado et al., 2006). In addition to these considerations, the genus Bothrops shows the greatest diversity when it comes to number of species, morphology and natural history characteristics ( Campbell and Lamar, 2004). Given these characteristics, the development of a polyvalent antivenom against accidents involving this genus is an even greater challenge. Thus, the production

of better antivenoms should take into consideration the quality of poisons, and what poisons should be used to compose the pool of immunization. Finally, the preclinical efficacy of the antivenom must be carefully evaluated. The inter specimen venom composition may be evidenced by the different levels of chymotrypsin-like activity and by the different potential GPX6 blockers obtained with the antibothropic serum and the five different Bothrops venoms studied in this paper. These venom composition variations may be an important factor to explain the failure of the antibothropic serum and, additionally, three other factors also may be responsible for the overall presented result. The first factor suggests a lack of immunoglobulins acting against serine peptidases present in some venoms and

the second factor may be related to the failure of blocking by the antibodies, although they may be present. The third and important factor may be related to degradation of the serine peptidases by the metallo peptidases before the inoculation of horses with the pool of venoms used for the production of antivenom, and this degradation could destroy the epitopes responsible for the production of immunoglobulins. These hypotheses are under investigation in our laboratories through new experiments, with the objective of developing strategies to obtain a more effective antibothropic serum. The antibothropic serum produced by the Butantan Institute is one of the best in Latin America to reduce mortality by snake poisoning from this genus.