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Toxic and enzymatic venom activities in mice and their neutralization assays 2.4.1. LD50s of Mlo venom, respectively. The amazing degree of conservation of immunogenic determinants between species of the clades of European and Oriental viper, which evolved geographically segregated since the early Miocene, suggests an eventual window of opportunity for the treatment of envenomings by Eurasian snakes. Clearly, the rational use of heterologous antivenoms requires establishing their para-specificity landscapes. This paper illustrates the analytical power of combining and preclinical quantitative assays toward this goal. Graphical abstract Open in a separate window 1.?Introduction Old World vipers (subfamily Viperinae within family Viperidae) are a group of venomous snakes endemic to Europe, Africa and Asia. Also known as true adders or viperines, these Eurasian snakes (extant genera and group (Laurenti, 1768) on three landmasses separated by the Mediterranean and Paratethys Seas, Europe, the Middle East and North Africa, during the early Miocene period (23.3C16.3 million years ago) (R?gl and Steininger, 1983; Szyndlar and Rage, 1999; Lenk et al., 2001, Garrigues et al., 2005). Present-day Old World snakes are distributed in a wide variety of habitats from North Africa to just within the Arctic Circle and from Great Britain to Pacific Asia (Mallow et al., 2003, Phelps, 2010). During the last decades the phylogeny of the polyphyletic group has undergone constant revision and divisions by a number of authors. Three major clades have been identified (Lenk et al., 2001, Garrigues et al., 2005), the European vipers (De Smedt, 2006, Kreiner, 2007); the oriental vipers, represented by i) the blunt-nosed subspecies (Linnaeus, 1758), (Chernov, 1940) (Terentiev and Chernov, 1940), (Dwigubsky, 1832), Rabbit Polyclonal to RASD2 (Chikin and Shcherbak, 1992), and (Nilson and Andrn, 1988); M. (Werner, 1935); and the recently described sp. n., with at least seven known representatives from central and southern Iran (Oraie et al., 2018), within the genus (Reuss, 1927, Herrmann et al., 1992); ii) the Mountain vipers of the complex (Nilson et al.,1999); and iii) a group of Asian and North African vipers within genus (Gray, 1842). The Dagestan blunt-nosed viper (Dwigubsky, 1832) is usually endemic to Asia. Having by far the widest range in central Asia, this large stout-bodied species, which can reach lengths of up to 1.7?m, is found in dry and well vegetated rocky mountainous areas between 1000 and 2500?m elevation from central Turkey through Syria, Lebanon, Iraq, northern Jordan, the Caucasus region (incl. Armenia), Azerbaijan, Dagestan, western and northwestern LDE225 Diphosphate Iran, southern Afghanistan, Pakistan and the Kashmir region (Mallow et al., 2003, Oraie et al., 2018). In Pakistan, is restricted to the western highlands, and is allopatric with in the Indus River valley (Khan, 1983). Crepuscular and nocturnal, but often abroad during daylight on overcast days, climb and forage in bushes. Adults feed primarily on small mammals, whereas young take mainly lizards (Phelps, 2010). The venom of the Dagestan blunt-nosed viper, a WHO category 2 species (Warrell, 2010), is highly potent. A mean dry venom yield of 48?mg per snake and intravenous (i.v.) LD50 of 12C18 g/18?g mouse body weight have been reported (Latifi, 1984, Kurtovi? et al., LDE225 Diphosphate 2014). Human envenomings by cause life-threating systemic hemodynamic disturbances, reduced functionality of the kidneys, and ischemia at the bite site (Schweiger, 1983, G??men et al., 2006, Sharma et al., 2008). Acute kidney injury is not common and if happens, is due to hypotension, and deposit of hemoglobin, myoglobin, and fibrin in the renal tubules causing acute tubular necrosis (Burdmann et al., 1993). However, information around the epidemiology of envenomings by across its distribution is usually scarce (Chippaux, 2012, Dehghani et al., 2014, Zamani et al., 2016) or non-existent. Treatment of snakebites envenomings is usually critically dependent on the availability of effective antivenoms. This study was LDE225 Diphosphate designed to assess a comparative preclinical efficacy of the monospecific anti-(anti-Mlt) antivenom manufactured by Uzbiopharm? (Uzbekistan) and the monospecific anti-antivenom from Microgen? (Russia) to neutralize key toxic effects of.