Summary
In order to obtain better insight into the potentiation of the toxicity of phospholipase A by crotapotin, we studied the distribution and elimination of these substances and of their combination.
Blood Plasma Concentration. Iodine-labelled phospholipase A leaves the bloodstream of mice and rabbits very quickly after i.v. application. Simultaneous injection of crotapotin speeds the elimination of the enzyme.
After subcutaneous application in mice the plasma concentration of phospholipase A depends on the quantity of enzyme injected. It is higher when the enzyme is complexed with crotapotin before injection. The plasma concentration of phospholipase A fails, however, to be proportional to the toxicity of the complex after subcutaneous application.
Crotapotin leaves the blood of mice also very quickly after i.v. application.
Organ Distribution. After i.v. application in mice, phospholipase A is heavily enriched in the liver. By simultaneous application of crotapotin, the enzyme is partially diverted to the kidneys. Only a small percentage of injected enzyme is found in the brain. This percentage is just significantly raised by simultaneous application of crotapotin. The diaphragm contains about the twofold amount of phospholipase A per wet weight as compared with other samples of skeletal musculature. With crotapotin, there is a slight increase of the radioactivity in all muscles investigated, with different degrees of significance.
Crotapotin is enriched in mouse kidneys after i.v. application.
Renal Elimination. The renal elimination of the acidic crotapotin is higher than that of the basic phospholipase A. In this respect, the latter resembles the basic polypeptide Trasylol®.
Doses of phospholipase A above 0.25 mg/kg cause intravital hemolysis. The hemolysis is prevented if a small amount of crotapotin is applied simultaneously.
Our findings show that the combination with crotapotin distinctly alters the pharmacokinetic behaviour of Crotalus terrificus phospholipase A. However, our data do not explain the tremendous increase of phospholipase A toxicity caused by the non-toxic crotapotin.
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Habermann, E., Walsch, P. & Breithaupt, H. Biochemistry and pharmacology of the crotoxin complex. Naunyn-Schmiedeberg's Arch. Pharmacol. 273, 313–330 (1972). https://doi.org/10.1007/BF00499666
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DOI: https://doi.org/10.1007/BF00499666