Dr. A. Leyva (USA) helped with English editing of the manuscript. “
“Envenoming by snakebites represents a relevant and neglected global health problem, particularly in tropical regions (Gutierrez et al., INNO-406 manufacturer 2006, Harrison et al., 2009 and Russell, 1991). Recent estimates indicate that at least 421,000 envenomations and 20,000

deaths related to ophidian accidents occur each year, mainly in Latin America, Asia and Africa (Kasturiratne et al., 2008); however, this same study suggests that these numbers can be as high as 1,841,000 envenomations and 94,000 deaths (Kasturiratne et al., 2008). Even so, the mortality caused by snakebite is much higher than the given by several neglected tropical diseases, such as dengue haemorrhagic fever, leishmaniasis, cholera, schistosomiasis

and Chagas disease, which leads the World Health Organization to include the ophidian accidents in the list of neglected tropical diseases (Williams et al., 2010). Snakes from Viperidae family selleck chemicals llc are found in many parts of the world causing several accidents every year (Gutierrez and Lomonte, 1995 and Kasturiratne et al., 2008). Particularly in Brazil, the majority of ophidian accidents occur with the Bothrops genus (Viperidae family) ( Rosenfeld and Kelen, 1971 and Saúde, 2001) that are characterized by pronounced local effects, including hemorrhage, edema, pain and myonecrosis ( Gutierrez and Chaves, 1980, Gutierrez and Ownby, 2003, Homsi-Brandeburgo et al., 1988, Mebs et al., 1983, Queiroz and Petta, 1984 and Rosenfeld and Kelen, 1971). These local effects are very relevant in terms of medical and scientific interest since the proteins responsible for the toxic process which may lead to permanent tissue loss, disability and, in some cases may require the amputation of the victim’s affected limb are not efficiently neutralized by

antivenom administration ( Gutierrez and Lomonte, 1995). Phospholipases A2 (PLA2s) are enzymes that catalyze the hydrolysis of glycerophospholipids, SSR128129E in a calcium-dependent manner, and represent the most abundant myotoxic components in Viperidae snake venoms (Gutierrez and Ownby, 2003). These proteins can be classified into two groups according to their evolutionary pathway: i) the catalytically active enzymes, such as Asp49-, Asn49- and Gln49-PLA2s and ii) the catalytically inactive PLA2 variants (Lys49-, Arg49-, and some Asp49-PLA2s) (dos Santos et al., 2011b). In this latter group, the most studied toxins are the basic and homodimeric Lys49-PLA2s that induce noticeable local myonecrosis by means of a calcium-independent mechanism (Lomonte and Rangel, 2012). In addition, Lys49-PLA2s exhibit some effects found exclusively in vitro, as the blockade of neuromuscular transmission in isolated preparations, which has been directly associated to their ability in destabilizing cell membranes ( Gallacci and Cavalcante, 2010 and Correia-de-Sa et al., 2013).