Non-neurotoxic activity of Malayan krait (Bungarus candidus) venom from Thailand

Background: Envenoming by kraits (genus Bungarus) is a medically significant issue in South Asia and Southeast Asia. Malayan krait (Bungarus candidus) venom is known to contain highly potent neurotoxins. In recent years, there have been reports on the non-neurotoxic activities of krait venom that include myotoxicity and nephrotoxicity. However, research on such non-neurotoxicity activities of Malayan krait venom is extremely limited. Thus, the aim of the present study was to determine the myotoxic, cytotoxic and nephrotoxic activities of B. candidus venoms from northeastern (BC-NE) and southern (BC-S) Thailand in experimentally envenomed rats. Methods: Rats were administered Malayan krait (BC-NE or BC-S) venom (50 g/kg, i.m.) or 0.9% NaCl solution (50 L, i.m.) into the right hind limb. The animals were sacrificed 3, 6 and 24 h after venom administration. The right gastrocnemius muscle and both kidneys were collected for histopathological analysis. Blood samples were also taken for determination of creatine kinase (CK) and lactate dehydrogenase (LDH) levels. The human embryonic kidney cell line (HEK-293) was used in a cell proliferation assay to determine cytotoxic activity. Results: Administration of BC-NE or BC-S venom (50 g/kg, i.m.) caused time-dependent myotoxicity, characterized by an elevation of CK and LDH levels. Histopathological examination of skeletal muscle displayed marked muscle necrosis and myofiber disintegration 24 h following venom administration. Both Malayan krait venoms also induced extensive renal tubular injury with glomerular and interstitial congestion in rats. BC-NE and BC-S venoms (1000.2 g/ mL) caused concentration-dependent cytotoxicity on the HEK-293 cell line. However, BC-NE venom (IC50 =8 ± 1 g/mL; at 24 h incubation; n = 4) was found to be significantly more cytotoxic than BC-S venom (IC50 =15 ± 2 g/mL; at 24 h incubation; n = 4). In addition, the PLA2 activity of BC-NE venom was significantly higher than that of BC-S venom...

Immunoreactivity and two-dimensional gel-electrophoresis characterization of Egyptian cobra venom proteome

The first and second [two] dimensional gel electrophoresis has a broad protein resolution power. It was used to separate and identify cobra venom proteome. The importance of characterizing venom proteins contents from the Egyptian elapidae, specifically neurotoxins, is based on the need to produce effective anti-venom. About 30-55distinct protein spots were identified on silver stained two-dimensional gels. Around two-thirds of the venom proteins displayed low a molecular weight and a migration into hydrophobic side. The venoms from Naja haja and Naja nigricollus showed 45-55 spots, while Walternnesia aegyptia had less [31-37] spots. The commercial prepared polyclonal antivenom had a strong signal for anionic and cationic venom protein spots with molecular weight 20-115 kDa. However, it showed weak or non immunoreactivity toward anionic low molecular weight spots [2.5-15kDa]. These results suggest the need to change the immunization schedule to include low molecular weight toxin-proteomes as separate dose or sequester injection

Micrurus spixii (Peruvian Coral Snake) venom-preliminary biochemical and enzymatic characterization

Micrurus spixii venom was studied after fractionation by Sephadex G-100 SF gel filtration chromatography. Several enzymatic activities and biological effects were investigated in whole venom and fractions. The venom was resolved in four peaks in a range of about 73.2-10.7 kDa molecular weight. Alkaline phosphatase and acetylcholinesterase activities were found in peak I, and procoagulant activity was seen in peak II. Phospholipase A2, hemorrhagic, and proteolytic activities were detected in peak III. A second procoagulant factor and proteinase were present in peak IV. Thrombin-like enzyme and direct hemolytic activities were not found in any assayed samples.

An in vitro study of the effects of venom of Australian elapids on murine skeletal muscle and the protective effect of homologous plasma

The venom of many dangerous Australian snakes has a myotoxic component and some are strongly myolytic. The myotoxicity of venom of seven Australian elapid snakes was studied to determine their relative in vitro potency in causing cell death of C2C12 cells, a myoblast cell line, and murine pmyotubes in mixed cell culture. The venom of Pseudechis australis proved to be most myotoxic, Austrelaps superbus and Pseudechis porphyriacus venoms also exhibited myotoxicity relative to the other venoms tested. The specificity of Pseudechis porphyriacus venom was tested using the human glioma cell line TC3 and was shown to exhibit a general cytotoxicity. Myotoxicity, however, was the predominant action of the venom. It has long been known that certain animals sucha as the mongoose (herpestes edwardsii) are able to survive envenomation. Some species of snakes also possess this property and the neutralising factor(s) responsible for this P. porphyriacus has been shown to be present in the serum. The protective effect of homologous plasma from P. porphyriacus venom was also studied with reference to myotoxicity and cytotoxicity. The results of this study clearly demonstrated protection by homologous plasma using a myoblast cell line, C2C12, a primary mixed cell culture and TC3 cells. While protection was clear, particularly using high concentrations of venom, it was not absolute, and homologous plasma did not afford continued protection from the effects of the venom. In the mixed culture experiments venom/plasma mixtures pre-incubated for 30 min were more protective than venom/plasma mixtures which were not incubated, in contrast to the results of cell culture studies, which showed little difference.

Do snake venom cytoloxins eschibit amphiphilicity?

It is suggested, on the basis of the structural information available from the literature, that the molecules of cobramine B and homologous cytotoxins, in contrast to snake venom neurotoxins, are amphiphilic in the sense that they are composed of a predominantly hydrophobic multi-stranded ß-sheet and other regions sharply hydrophilic. It is possible that the direct lytic activity of snake venom cytotoxins is due, at least in part, to their amphiphathy

Phylogenetic relationships of snake venom toxic proteins

Two kinds of distance matrices have been formed from minimum mutational distances and absolute hydrophobicity differences obtained by comparison of aligned homologous sequences of 56 toxins from venom os snakes belonging to 7 genera. Phylogenetic trees were constructed from these distance matrices, employing the unweighted pair-group method using arthmetic averages (UPGMA). The Pearson product-moment correlation coefficient has been used to estimate the agreement between the original distance matrix and that obtained directly from the dendrogram. For al these procedures the set of computer programs PHYTREE (written in BASIC for micro-computer, and available from the author) has been used