Detoxified venom from Crotalus durissus terrificus is devoid of cytotoxic activity and induces mitogenesis

The venom from the snake Crotalus durrissus terrificus was detoxified by stepwise incorporation of stable cationic iodine. The venoid, in a dosage equivalent to 100 LD50 of the letal venom, was injected in mice without lethal exits. The native venom (NAT), or its toxoided (TXD) derivative were incubated in presence or absence of mitogens, with human mononuclear (MN), B and T cells, with a pulse of [3H]Thymidine. No synergistic or antagonistic effects were observed in the combined activity of the mitogens and NAT or TXD. In the direct action of NAT the incorporation of radioactivity into MN and T cells diminished with venom increase in concentration indicating that the cytotoxicity of the native venom was correlated with the amount added. With B cells, the native venom exercised an initial mitogenic activity, declining in the higher concentration. On the other hand, the TXD showed a consistent effect, increasing the thymidine uptake in a manner related to concentration. This stimulation by TXD was observed with all groups of cells. The results indicate that, by abolishing direct cytotoxic activity with toxoiding of this venom, a derivative that enhances mitogenesis in these white cells can be obtained.