Chemonucleolytic effects of chondroitinase ABC on normal rabbit intervertebral discs. Course of action up to 10 days postinjection and minimum effective dose.
METHODS
This study demonstrated the chemonucleolytic effects of chondroitinase ABC and its histologic and biochemical background.


OBJECTIVE
To determine the course of chondroitinase ABC action on normal rabbit discs, and to find its minimum effective dosage.


BACKGROUND
No previous study has assessed the chemonucleolytic action of chondroitinase ABC in a time- and dose-dependent manner. This study also investigated the biochemical causes of radiologic and histologic changes in the discs.


METHODS
Rabbits were injected with 4 U of pharmaceutical-grade chondroitinase ABC intradiscally. They were radiologically and histologically observed, and biochemical analyses of the discs were conducted on days 1, 3, 5, 7, and 10 postinjection in the time course study. Different doses of chondroitinase ABC were injected, and radiologic observations and water content of the discs were measured in the dose-finding study.


RESULTS
The time course study revealed that the chondroitin sulfate content of discs significantly decreased from day 1 postinjection until the end of the experimental period. The weight and water content of the nucleus pulposus decreased on day 3, and disc space narrowing was observed from the day after injection. The dose-finding study showed that a dose of 0.0002 U/disc still induced disc space narrowing and a decrease in water content.


CONCLUSIONS
Chondroitinase ABC is estimated to have a chemonucleolytic effect at least by day 3 postinjection at a dose level of 0.0002 U/disc or higher in rabbits.
Takahashi
T
T
Tokyo Research Institute, Seikagaku Corporation, Japan.
Kurihara
H
H
Nakajima
S
S
Kato
T
T
Matsuzaka
S
S
Sekiguchi
T
T
Onaya
M
M
Miyauchi
S
S
Mizuno
S
S
Horie
K
K
Fujita
Y
Y
Hirose
T
T
D000818:Animals; D002808:Chondroitin Lyases / Q000378:metabolism / Q000494:pharmacology*; D002809:Chondroitin Sulfates / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006820:Hyaluronic Acid / Q000378:metabolism; D007403:Intervertebral Disc / Q000737:chemistry / Q000000981:diagnostic imaging / Q000187:drug effects*; D007404:Intervertebral Disc Chemolysis; D007632:Keratan Sulfate / Q000378:metabolism; D009929:Organ Size; D011817:Rabbits; D011859:Radiography; D013997:Time Factors; D014867:Water / Q000378:metabolism
D014867:Water; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D007632:Keratan Sulfate; D002808:Chondroitin Lyases