title: In vitro cytoprotective effects of acetylsalicylic acid, carprofen, meloxicam, or robenacoxib against apoptosis induced by sodium nitroprusside in canine cruciate ligament cells.
abstract: OBJECTIVE
  To determine whether incubation of cruciate ligament cells with acetylsalicylic acid, carprofen, meloxicam, or robenacoxib provides protection against apoptosis induced by sodium nitroprusside (SNP).
  
  
  METHODS
  Explants of cranial (CCL) and caudal (CaCL) cruciate ligaments from eight 1-day-old Beagles.
  
  
  METHODS
  Primary cultures of CCL and CaCL cells were created via enzymatic dissociation of cruciate explants. Purified cell cultures were incubated for 2 hours without (controls) or with 1 of 3 concentrations of 1 of 4 NSAIDs (10, 100, or 200 μg of acetylsalicylic acid/mL; 0.1, 1, or 10 μg of carprofen/mL; 0.1, 1, or 10 μg of meloxicam/mL; or 0.1, 1, or 10 μg of robenacoxib/mL) and subsequently incubated for 18 hours with 1 of 3 concentrations of SNP in an attempt to induce mild, moderate, or severe cytotoxic effects. Cell viability and apoptosis were analyzed via a cell proliferation assay and flow cytometry, respectively. Prostaglandin E(2) concentrations were measured via an ELISA.
  
  
  RESULTS
  Cytoprotective effects of NSAIDs were dependent on the extent of SNP-induced apoptosis and were greatest in CCL and CaCL cell cultures with moderate SNP-induced cytotoxic effects. Preincubation with an NSAID improved cell viability by 15% to 45% when CCL and CaCL cells were subsequently incubated with SNP. Carprofen (10 μg/mL) had the greatest cytoprotective effects for CCL and CaCL cells. Incubation with NSAIDs resulted in a nonsignificant decrease in PGE(2) production from SNP-damaged cells.
  
  
  CONCLUSIONS
  Results indicated that carprofen, meloxicam, and robenacoxib may reduce apoptosis in cells originating from canine cruciate ligaments.
authors.affiliation: Division of Small Animal Surgery and Orthopedics, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.
authors.forename: Katrin
authors.initials: K
authors.lastname: Waldherr
authors.forename: Andreas
authors.initials: A
authors.lastname: Zurbriggen
authors.forename: David E
authors.initials: DE
authors.lastname: Spreng
authors.forename: Simone
authors.initials: S
authors.lastname: Forterre
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000166:cytology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D019610:Cytoprotection; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009569:Nitric Oxide; D009599:Nitroprusside / Q000633:toxicity*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009599:Nitroprusside; D009569:Nitric Oxide