ABSTRACT
The effect of recombinant microplasmin (micro-plasmin) on acute cerebral infarction was evaluated in rats, and compared with recombinant tissue plasminogen activator (rt-PA). After the model of middle cerebral artery occlusion (MCAO) was established by autologous blood clots, different doses of micro-plasmin (2.5, 5, and 10 mg x kg(-1)) were administered into the thrombus intra-arterial. Twelve hours after administration of micro-plasmin, the neurological deficit score of rats was recorded and the infarct volumes were determined. Bleeding time (BT), fibrin degradation product (FDP) concentration in serum and thrombin time (TT), prothrombin time (PT) and fibrinogen (FIB) concentration in plasma were tested after administration. Intra-arterial administration of micro-plasmin could reduce significantly neurological deficit score and infarct volumes in MCAO rats. FDP concentration increased significantly as compared with model group. There were no significant differences in TT, PT and BT. FIB concentration reduced markedly as compared with model group, but had no significant difference as compared with sham group. The results suggest that micro-plasmin is effective in treatment of rat acute cerebral infarction, and has no significant influence on fibrinolytic system and blood clotting system, indicating that micro-plasmin may be useful for treatment of acute cerebral infarction, and not lead to hemorrhage. Micro-plasmin seems to be distinguished from clinical used rt-PA by its no hemorrhage effect.
Subject(s)
Animals , Male , Rats , Bleeding Time , Brain , Pathology , Cerebral Hemorrhage , Metabolism , Pathology , Cerebral Infarction , Drug Therapy , Pathology , Fibrin Fibrinogen Degradation Products , Metabolism , Fibrinogen , Metabolism , Fibrinolysin , Pharmacology , Infarction, Middle Cerebral Artery , Peptide Fragments , Pharmacology , Prothrombin Time , Random Allocation , Rats, Sprague-Dawley , Recombinant Proteins , Pharmacology , Thrombin Time , Tissue Plasminogen Activator , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To extract and purify ricin from castor beans and to evaluate its anti-cancer activity.</p><p><b>METHODS</b>Ricin was purified from castor beans according the modified method of Nicolson and Blaustin. The lectins were extracted in 0.01 mol/L phosphate buffered saline and isolated in the 40% to 80% fraction of ammonium sulfate precipitation. The dialyzed fractionated preparation was applied with a Sepharose 4B column. The lectins were eluted with a linear lactose gradient (0.01 mol/L approximately 0.5 mol/L). Ricin was separated from the ricinus agglutinin by gel filtration on a Sephadex G-100. MTT was applied to analyze the cytotoxicity with different dosage of ricin in different cancer cell lines.</p><p><b>RESULTS</b>There was no difference between the killing effect of normal cells and that of colon cancer cells by using the high dosage of ricin (5 x 10(-8) mol/L approximately 5 x 10(-10) mol/L). However, the cytotoxicity was significant different in those cells with the low dosage of ricin (5 x 10(-11) mol/L approximately 5 x 10(-13) mol/L). Meanwhile ricin had the similar cytotoxicity to leukemia cell K562 and colon cancer cell SW480.</p><p><b>CONCLUSION</b>Ricin is able to kill tumor cells selectively at low concentration, but the selectivity does not appear at high concentrations.</p>