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

The mechanism of action underlying chymopapain (Chymodiactin) chemonucleolysis remains obscure. Radiographic studies suggest that chymopapain does not alter disc fragment size acutely; nonetheless, patients often report symptom resolution within a few days, even hours, of treatment. The authors postulate that, in addition to its chemonucleolytic action, chymopapain may possess antiinflammatory properties. To test this hypothesis, the authors assessed the ability of chymopapain to modulate the activity of the proinflammatory enzyme phospholipase A2 (PLA2) and to ameliorate behavioral changes associated with inflammatory neuropathy in an in vivo model of sciatica. Thirty-nine male Fischer rats were randomly assigned to one of three treatment groups: 1) saline, 2) betamethasone, or 3) chymopapain. All of the rats underwent unilateral sciatic nerve ligation with loose chromic gut suture to induce inflammatory mononeuropathy. The animals were tested for thermal and mechanical hyperalgesia on Days 0 (preoperation), 7 (pretreatment), and 14 (prior to death). Three animals were killed on Day 0 to determine the baseline PLA2 activity within unmanipulated rat sciatic nerves. On Day 7, three animals from each group were killed to assess PLA2 activity prior to treatment. The remainder were given a single infusion of saline, betamethasone (0.3 mg/kg), or chymopapain (100 pKat U) around the inflamed nerve. On Day 14, the remaining animals were killed and their sciatic nerves were removed. The tissue was homogenized and the PLA2 activity was determined using [14C]arachidonate-labeled Escherichia coli phospholipid membrane as a substrate. Lipids were extracted and separated by thin-layer chromatography. All animals developed behavioral changes consistent with inflammatory mononeuropathy 24 to 72 hours postoperatively; these included gait disturbance, flexion deformity, and hyperalgesia of the involved hindlimb. The degree of mechanical and thermal hyperalgesia was comparable between groups at Day 7. By Day 14, the thermal hyperalgesia had resolved; the mechanical hyperalgesia was less evident in the betamethasone- and chymopapain-treated groups than in the saline-treated controls (p = 0.003; saline- vs. chymopapain-treated groups p = 0.004; saline- vs. betamethasone-treated groups p = 0.008). The mean PLA2 activity at baseline (Day 0) was 11.6 +/- 4.9 nmol phospholipid hydrolyzed per minute per milligram of protein. The PLA2 activity at Day 7 was 74.4 +/- 18.2 (ligated side) and 21.2 +/- 11.7 (nonligated side). At Day 14, PLA2 activity was reduced in the chymopapain- (47.8 +/- 12.3) and betamethasone- (39.7 +/- 9.5) treated groups compared with the saline control group (62.3 +/- 11.2), (saline- vs. chymopapain-treated groups p < 0.05; saline- vs. betamethasone-treated groups p < 0.01). The PLA2 activity in nonligated specimens was 18.6 +/- 10.1. These data indicate that chymopapain exhibits antiinflammatory properties in vivo, reducing PLA2 activity and ameliorating mechanical hyperalgesia in this model of inflammatory sciatic neuropathy.
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PMID:Chymopapain-induced reduction of proinflammatory phospholipase A2 activity and amelioration of neuropathic behavioral changes in an in vivo model of acute sciatica. 917 Nov 79

Current control of gastrointestinal nematodes relies primarily on the use of synthetic drugs and encounters serious problems of resistance. Oral administration of plant cysteine proteinases, known to be capable of damaging nematode cuticles, has recently been recommended to overcome these problems. This prompted us to examine if plant cysteine proteinases like the four papaya proteinases papain, caricain, chymopapain, and glycine endopeptidase that have been investigated here can survive acidic pH conditions and pepsin degradation. The four papaya proteinases have been found to undergo, at low pH, a conformational transition that instantaneously converts their native forms into molten globules that are quite unstable and rapidly degraded by pepsin. As shown by activity measurements, the denatured state of these proteinases which finally results from acid treatment is completely irreversible. It is concluded that cysteine proteinases from plant origin may require to be protected against both acid denaturation and proteolysis to be effective in the gut after oral administration.
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PMID:Structural characterization of the papaya cysteine proteinases at low pH. 1643 27