Inhibition of Myotoxic Activity of Bothrops asper Myotoxin II by the Anti-trypanosomal Drug Suramin

Bothrops snake myotoxins induce a large efflux of ATP and potassium with spreading of cell damage and pain

“…The present data also provide an additional explanation to the finding that the antitrypanosomal drug suramin protects from the toxic effects of the Lys49 myotoxins of the Bothrops jararacussu and Bothrops asper venoms (47). This was explained previously as a direct neutralization of the myotoxin by formation of a suramin-myotoxin complex (48). However, suramin also binds to P2X channels (32), and this property could, at least in part, account for suramin inhibitory activity because it would prevent the ATP-dependent spreading effect of the injected myotoxin.…”

Low-level laser therapy decreases local effects induced by myotoxins isolated from Bothrops jararacussu snake venom

“…Neutralization of snake venoms and isolated toxins by plant extracts has been extensively explored as an alternative treatment to serum therapy (17,18,44). Natural and synthetic compounds such as heparin, suramin, fucoidan and animal serum factors have also been studied (45)(46)(47)(48)(49)(50)(51).…”

Crystallization and preliminary X-ray diffraction analysis of a novel Arg49 phospholipase A2homologue fromZhaoermia mangshanensisvenom

“…The atomic coordinates of the Lys49 PLA 2 from Bothrops asper venom, which displays a sequence identity of 70%, were used to generate a search model (Murakami et al, 2005; PDB code 1y4l) and molecular-replacement calculations were carried out using the program AMoRe in the resolution range 25.0-4.0 Å (Navaza, 1994). A clear solution was obtained for two molecules in the asymmetric unit in space group P6 4 .…”

“…Despite their catalytic inactivity, Lys49 PLA 2 s are very potent in the induction of myonecrosis, a major and clinically highly challenging event in envenomation by most viperid snakes, based on one or more mechanisms that continue to be enigmatic to toxinologists. Consequently, a number of different strategies, such as structural analysis (Arni & Ward, 1996;Ownby et al, 1999;Murakami & Arni, 2003), chemical modification (Andriã o-Escarso et al, 2000;Soares et al, 2001), sequence-comparison analyses (Selistre de Araujo et al, 1996;Ward et al, 1998), charge-distribution analysis (Kini & Iwanaga, 1986;Kini & Evans, 1989), hydrophobicity profiles (Kini & Iwanaga, 1986), synthetic peptide studies (Lomonte et al, 1994;Nuñ ez et al, 2001) and site-directed mutagenesis (Ward et al, 2002), have attempted to elucidate the structural determinants for the myotoxicity expressed by Lys49 PLA 2 s. The three-dimensional structures of a large number of Lys49 PLA 2 s in both native and complexed states have recently been elucidated (Arni et al, 1995;Lee et al, 2001;Ambrosio et al, 2005;Murakami et al, 2005Murakami et al, , 2006Murakami et al, , 2007 and have contributed to addressing the role of Lys122 in the myotoxicity of Lys49 PLA 2 s (Ambrosio et al, 2005;Watanabe et al, 2005).…”

“…Compounds such as suramin, heparin, heparin-like glycosaminoglycans, related polyanions and polyethylene glycol derivatives have been shown to effectively inhibit the activity of myotoxic Lys49 PLA 2 s both in vitro and in vivo (Murakami et al, 2005(Murakami et al, , 2007. Recently, a new role has been proposed for Lys49 PLA 2 s in the inhibition of the vascular endothelial growth factor and its receptor system, which plays a central role in angiogenic processes (Yamazaki et al, 2005).…”