Hemorrhagic changes and microglia activation induced by Macrovipera lebetina obtusa venom with the inhibited enzymatic activity in rat brain

The metalloproteinases and phospholipase A(2) are the main enzymes in the venom of Macrovipera lebetina obtusa that play a decisive role in the destructive and toxic effects on the organism of the prey. Metalloproteinases cause hemorrhagic damage, destroy the basement membrane of the blood vessel and disrupt the connections between endothelial cells. Phospholipase A2 causes hemolysis of erythrocytes, destroy the cell membranes, and inhibits the adhesion of platelets and so on. The state of the capillaries of the rat brain and microglia under the action of the venom with separately inhibited enzymes was investigated and compared to the action of the crude venom. Also, the toxicity LD50 of the venom of Macrovipera lebetina obtusa with the inhibited enzymatic activity was determined. The histochemical study showed that the inhibition of phospholipase A(2) enzymatic activity did not significantly change the vasodestructive effect of the venoms. In case of action of a venom with inhibited enzymatic activity of metalloproteinases, low activity of microglia and less damaged capillaries were observed. The toxicity of the venom with inhibited phospholipase A(2) and with inhibited metalloproteinases was respectively 1.8 and 3.7 times weaker than that of the crude venom. We can claim that both the toxicity of the venom of Macrovipera lebetina obtusa, the damaged brain vessels and the increased activity of CNS microglia are determined mainly by the action of metalloproteinases.