, 2006). Until now, the main component with high in vitro hemolytic activity isolated from this venom was the phospholipase A2 enzyme, although the presence of proteolytic selleck enzymes that act specifically on the membrane glycoproteins of erythrocytes cannot be ruled out ( Seibert et al., 2006 and Seibert et al., 2010). Since myotoxins are commonly described in several snake, spider and bee venoms, the presence of myotoxic activity

in L. obliqua was investigated using specific biochemical markers, in vitro experiments and histological analyses. In this sense, elevations of serum CK and CK-MB activities were detected, indicating systemic damage to skeletal and cardiac muscles. Cell Cycle inhibitor CK is a dimer with M and

B subunits that is found primarily in the muscle, myocardium, brain and lung tissues and exists as three dimeric isoenzymes: CK-MM, CK-MB and CK-BB. CK-MB accounts for 5%–50% of total CK activity in the myocardium and is well-established to be a clinical marker that can confirm acute myocardial infarction both in humans and experimental animals ( Apple and Preese, 1994 and Shashidharamurthy et al., 2010). Correlated with the increases in CK and CK-MB, histological analyses revealed extensive muscle damage mainly in the subcutaneous tissue (at the local site of venom injection) and myocardial necrosis. These observations support the idea that the LOBE has cardiotoxic activity, which was unknown up until now. Clinical reports of human envenomation that are available in the literature do not describe symptoms of cardiac dysfunction, Coproporphyrinogen III oxidase and CK or CK-MB levels are rarely measured in these patients, making it difficult to make any comparisons with our experimental data. Our hypothesis is that the contribution

of muscle damage observed herein is more related to myoglobin release from the myocytes or cardiomyocytes than to a mechanism that is associated with heart dysfunction. Indeed, similar to hemoglobin, myoglobin can also precipitate in renal tubules, after being filtered by the glomeruli, and forms obstructive casts. The direct myotoxic activity of LOBE was confirmed in vitro by the experiments with isolated EDL muscles. LOBE showed a dose- and time-dependent myotoxicity in isolated EDL, although its potency was lower when compared to B. jararaca venom. In fact, different myotoxins have been described in B. jararaca venom, including metalloproteinases and myotoxic phospholipase A2 ( Zelanis et al., 2011), while in L. obliqua the toxins responsible for this activity remain completely unknown. However, L. obliqua myotoxins seem to be recognized by ALS because treatment with this serum was able to reverse CK release in vitro (from EDL muscle) and in vivo if administered within 2 h of envenomation.

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