Partial purification and some physicochemical properties of phospholipases A2 from the venom of the bushmaster snake (Lachesis muta)

Screening of the biochemical-pharmacological properties of the crude venom from the snake Lachesis muta indicated the presence of phospholipase A2 (PLA2; 5260 U/mg protein), procoagulant (2630 U/mg protein), platelet aggregating (43 U/mg protein) and caseinolytic activities (6670 U/mg protein). These activities were separated by filtration of the crude venom on Sephacryl S-200. The material containing PLA2 activity was further fractioned by DEAE-cellulose ion exchange chromatography into four active fractions (F-I to F-IV, containing 1.7, 1.2, 0.3, and 0.05 per cent of the crude venom protein, respectively) by stepwise elution with buffers of increasing ionic strength. All fractions presented a molecular weight of approximately 15,000 and isoelectric points in the range pH 4.6-6.0. In addition to their indirect hemolytic activity, the partially purified fractions inhibited platelet aggregation induced either by collagen or thrombin. p-Bromophenacyl bromide-treated fractions lost both phospholipase A2 activity and their inhibitory effect on collagen-induced platelet aggregation

Antitumor effects of dopaminergic blockers in mice bearing ehrlich tumors

We determined the effect of 13 days of treatment with 2.0 mg/kg haloperidol, 30.0 mg/kg metoclopramide or 4.0 mg/kg domperidone on the number of tumor cells of mice bearing Ehrlich ascites carcinoma. The three dopaminergic blockers significantly reduced the number of tumor cells of experimental mice. The mean ñ SEM number of tumor cvells x 10******6/ml saline lavage was 25.5 ñ 5.9 for the haloperidol group, 36.8 ñ 4.7 for the metoclopramide group, 25.3 ñ 3.5 for the domperidone group and 54.0 ñ 9.0 for the control mice (treated with 0.9% NaCl). In a second experiment, treatment with 0.5 and 2.0 mg/kg haloperidol showed that the antitumor effect of this drug was dose dependent. The possible mechanisms underlying these results (such as an increase in prolactin levels or a direct action of these drugs on lymphocytes) are discussed in light of the specific pharmacological properties of each dopaminergic blocker

Biochemical and pharmacological screening of snake (Bothrops) venoms: characterization of components acting on blood coagulation and platelet aggregation

Six venoms from snakes of the genus Bothrops were tested for coagulation, platelet aggregation and phospholipase A2 (PLA2) activity. Almost all showed pro-coagulant and PLA2 activities while pro-aggregating properties were found only for some venoms. Bothrops jararaca venom showed different protein peaks associated with these activities. The pro-aggregating activity was inhibited by EDTA, leupeptin and mepacrine while the PLA2 activity was blocked by p-bromophenacyl bromide and 2-mercaptoethanol. Venom screening tests for clotting and platelet aggregation may represent a valuable tool for snake taxonomy and for monitoring the quality of antisera