Clearance and distribution of a haemorrhagic factor purified from Bothrops jararaca venom in mice

M. Tanigawa , M. Maruyama , M. Sugiki , K. Shimaya , K. Anai and H. Mihara . Clearance and distribution of a haemorrhagic factor purified from Bothrops jararaca venom in mice. Toxicon 32, 583–593, 1994.—We previously purified two fibrinolytic/haemorrhagic enzymes (jararafibrase-I and II) from Bothrops jararaca venom. In the present study, the clearance, organ distribution and local absorption rate were examined in mice using 125 I-labelled jararafibrase-I. Following intravenous injection of 125 I-labelled jararafibrase-I, a complex was rapidly formed with the plasma protein and the radioactivity quickly disappeared from the circulation with a half-life of about 3 min for the initial part of the curve. The highest level of the radioactivity (59.5%) was seen 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. At 60 min after dosing, 36.8% of the total injected radioactivity was seen in the contents of the small intestine, and 11.4% of the total injected radioactivity was seen in the contents of the large intestine at 120 min after dosing. It is assumed that the jararafibrase-I was metabolized mainly in the liver, to small mol. wt products, and excreted in the intestine via the bile duct. Also, a small amount of jararafibrase-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 flow caused by subcutaneous haemorrhage.