Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.6 (chymopapain)
 407 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevated serum levels of keratan sulfate (KS) and hyaluronate (HA) in patients with osteoarthritis (OA) have been reported. We measured KS and HA in dogs to determine if there was an elevation of these serum glycosaminoglycans in a canine model of OA. A single intraarticular injection of 1 mg of chymopapain into a shoulder joint increased serum KS by tenfold, and HA by less than twofold, in 24 hours. Serum KS and HA levels were 3-5-fold higher in dogs younger than 2 months of age than in older dogs. Serum KS and HA concentrations and synovial fluid KS concentrations were unrelated to spontaneous cartilage degeneration in 1-year-old dogs. Higher KS levels in synovial fluid correlated with higher KS levels in serum (r = 0.54, P less than 0.025). The mean KS concentration in sera of older dogs (greater than 3 years old) with OA was 37% higher than that in disease-free controls, but the difference between the groups was not statistically significant. Thus, elevated levels of serum KS and HA do not appear to have clinical significance in this model of OA.
 ...
PMID:Canine serum keratan sulfate and hyaluronate concentrations. Relationship to age and osteoarthritis. 252 84

The injection of 2.0 mg chymopapain into the adolescent rabbit knee causes severe loss of articular cartilage proteoglycans (PG). Although chondrocytes attempt to restore lost PG, failure to repair ensues. Pure chondroitin 4,6-sulfate (Condrosulf, IBSA Lugano, Switzerland) has been used in clinical studies of human osteoarthritis (OA) as a slow-acting drug for OA (SYSADOA). Using our model of articular cartilage injury, we examined the effects of oral and intramuscular administration of Condrosulf after chymopapain-induced cartilage injury. In this study, animals received an injection of 2.0 mg chymopapain (Chymodiactin, Boots Pharmaceuticals) into the left knee and were sacrificed after 84 days. The contralateral right knee served as a noninjected control. Some animals received oral Condrosulf while others received intramuscular injections of Condrosulf. Serum keratan sulfate (KS) levels were monitored to ensure degradation of the cartilage PG. Those animals not exhibiting at least a 100% increase of serum KS following chymopapain injection were excluded from the study. At sacrifice, cartilage PG contents were markedly reduced in animals receiving an injection of 2.0 mg chymopapain with no further treatment. In contrast, oral administration of Condrosulf beginning 11 days prior to chymopapain injury resulted in significantly higher (P = 0.0036) cartilage PG contents. Intramuscular administration of Condrosulf resulted in higher, but less significantly so (P = 0.0457), cartilage PG contents. These results suggest that daily Condrosulf treatment prior to and continuing after chymopapain injury may have a protective effect on the damaged cartilage, allowing it to continue to re-synthesize matrix PG after the treatment is discontinued.
Osteoarthritis Cartilage 1998 May
PMID:Protective effect of exogenous chondroitin 4,6-sulfate in the acute degradation of articular cartilage in the rabbit. 974 13

To measure urinary levels of two pyridinium cross-links of collagens at various times, rabbits were injected in the left knee with 0.2 mg (N = 11) or 2.0 mg chymopapain (N = 11). Urinary levels of the bone-specific deoxy-pyridinoline cross-link and of the hydroxylysyl pyridinoline cross-link, found in large amounts in articular cartilage and bone, were measured by high performance liquid chromatography (HPLC). The urinary levels were correlated with histological evidence of progressive articular cartilage destruction in animals injected with 2.0 mg chymopapain and of successful repair in rabbits injected with the lower dose. Rabbits injected with 2.0 mg chymopapain showed a very large increase in urinary levels of deoxy-pyridinoline during the first 30 days after the injection. This rise was not seen in animals injected with the lower dose. A rise in urinary level of the hydroxylysyl pyridonline cross-link was observed in all rabbits but was more pronounced and lasted longer in animals receiving the higher dose. The failure of rabbits injected with 2.0 mg chymopapain to repair the damaged articular cartilage was strongly associated with a marked increase in the catabolism of the bone-specific deoxy-pyridinoline cross-link and to a lesser extent with the catabolism of the hydroxylysyl pyridinoline found in bone and in articular cartilage.
Osteoarthritis Cartilage 1993 Jul
PMID:Elevation in urinary levels of pyridinium cross-links of collagen following chymopapain-induced degradation of articular cartilage in the rabbit knee provides evidence of metabolic changes in bone. 1544 25