The dose-related effects of phenylbutazone and a methylprednisolone acetate formulation (Depo-Medrol) on cultured explants of equine carpal articular cartilage.
The dose-related effects of phenylbutazone and Depo-Medrol on chondrocyte viability and chondrocyte-mediated synthesis and depletion of proteoglycans were investigated using cultured explants of equine middle carpal joint articular cartilage. Explants from 12 horses (941 x 3 mm diameter) were cultured for a total of 5 days, which included 3 days' exposure to either phenylbutazone (0, 2, 20, 200 or 2000 micrograms/mL) or Depo-Medrol (0, 20, 200 or 2000 micrograms/mL). For each explant, amino sugar content was used as a measure of proteoglycan content, 35S incorporation as a measure of the rate of proteoglycan synthesis and the number of pyknotic nuclei as a measure of cell death. During culture, control explants remained metabolically active and viable but suffered a net loss of proteoglycans. Proteoglycan loss was reduced by the presence of either phenylbutazone or Depo-Medrol. This effect was significant at clinically relevant concentrations of phenylbutazone (2-20 micrograms/mL), but not Depo-Medrol (20-200 micrograms/mL). Depo-Medrol caused a dose-dependent suppression of proteoglycan synthesis at all concentrations, but chondrocyte viability was affected only at the 2000 micrograms/mL dose. Phenylbutazone affected proteoglycan synthesis and cell viability only at the 2000 micrograms/mL concentration. At all concentrations, the anticatabolic effects of each drug influenced the proteoglycan content of the explants far more than did any antianabolic or cytotoxic drug effect. The results suggest that the therapeutic potential of both phenylbutazone and Depo-Medrol may not be restricted to their anti-inflammatory effects on the soft tissues of the joint.
Jolly
W T
WT
Department of Physiology and Anatomy, Massey University, Palmerston North, New Zealand.
Whittem
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Jolly
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Firth
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EC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002350:Carpus, Animal; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D006736:Horses; D008775:Methylprednisolone / Q000494:pharmacology*; D010653:Phenylbutazone / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011509:Proteoglycans; D010653:Phenylbutazone; D008775:Methylprednisolone