Study of blood metabolism and urinary excretion of chymopapain following intradiscal injection using a high-sensitivity enzyme immunoassay.

To develop chymopapain-induced chemonucleolysis as an established treatment, it is necessary to determine the kinetics of chymopapain in blood and urine following intradiscal injection. To investigate the rate of blood metabolism and urinary excretion of chymopapain following intradiscal injection, we developed a high-sensitivity enzyme immunoassay for chymopapain. The sensitivity for this assay was 1 pg/tube (40 amol). After injecting chymopapain into the nucleus pulposus of humans, levels of blood chymopapain were measured by enzyme immunoassay. The level of chymopapain in blood decreased gradually, with a half-life of 2-3 days. The half-life for urinary excretion was a little longer, at 3 days. It was also found that chymopapain in blood was not present as a free molecule but formed a complex that had a molecular weight of about 120 kDa. These findings suggest that most chymopapain would not have activity in blood.

Alteration and recovery of the spatial orientation of the collagen network of articular cartilage in adolescent rabbits following intra-articular chymopapain injection.

We have used polarized light (POL) to monitor changes in the organization of the articular cartilage collagen network and matrix proteoglycans (PGs) after intra-articular injection of chymopapain (CP). POL viewing of sirius red stained sections revealed a loss of normal birefringence suggesting an apparent collapse of the collagen network following intra-articular CP. After 21 days, knees injected with 2.0 mg CP showed no return of normal birefringence, however, normal birefringence was noted in knees injected with only 0.2 mg CP. POL viewing of toluidine blue stained sections revealed a severe loss of matrix PGs followed by PG restoration in animals injected with 0.2 mg CP. The most important inference from the data is that articular cartilage can recover from enzyme-induced alterations in the spatial collapse of its fibrillar network. This is an important finding since it has often been inferred that damage to the collagen network leads invariably to progressive articular cartilage destruction.