ABSTRACT
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
Subject(s)
Animals , Phospholipases A/isolation & purification , Viper Venoms/chemistry , Chromatography, Gel , Chromatography, Ion Exchange , Phospholipases A/pharmacology , Platelet Aggregation , Viper Venoms/enzymology , Viper Venoms/metabolism , ViperidaeABSTRACT
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
Subject(s)
Animals , Mice , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carcinoma, Ehrlich Tumor/drug therapy , Analysis of Variance , Domperidone/administration & dosage , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Haloperidol/administration & dosageABSTRACT
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