CLEARANCE AND DISTRIBUTION OF A HEMORRHAGIC FACTOR PURIFIED FROM BOTHROPS-JARARACA VENOM IN MICE

We previously purified two fibrinolytic/haemorrhagic enzymes (jararafi brase-I and II) from Bothrops jararaca venom. In the present study, th e clearance, organ distribution and local absorption rate were examine d in mice using I-125-labelled jararafibrase-I. Following intravenous injection of I-125-labelled jararafibrase-I, a complex was rapidly for med with the plasma protein and the radioactivity quickly disappeared from the circulation with a half-life of about 3 min for the initial p art of the curve. The highest level of the radioactivity (59.5%) was s een in the liver at 5 min after dosing, and the next highest level of radioactivity (14.4%) was seen in the kidney at 60 min after dosing. A t 60 min after dosing, 36.8% of the total injected radioactivity was s een in the contents of the small intestine, and 11.4% of the total inj ected radioactivity was seen in the contents of the large intestine at 120 min after dosing. It is assumed that the jararafibrase-I was meta bolized mainly in the liver, to small mol. wt products, and excreted i n the intestine via the bile duct. Also, a small amount of jararafibra se-I appeared to be metabolized in the kidney. Following subcutaneous injection, a high-dose group revealed a low local absorption rate. The low local absorption rate was apparently due to a diminished blood fl ow caused by subcutaneous haemorrhage.