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Expression of the cyclooxygenase isoforms in the prodromal stage of black walnut-induced laminitis in horses

R. Wayne Waguespack DVM, MS1,2, Anne Cochran BS3, and James K. Belknap DVM, PhD4,5
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  • 1 Department of Clinical Science, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.
  • | 2 Present address is the Department of Clinical Science, College of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
  • | 3 Department of Clinical Science, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.
  • | 4 Department of Clinical Science, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.
  • | 5 Present address is the Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210.

Abstract

Objective—To compare the levels of mRNA expression of cycooxygenase (COX)-1 and COX-2 in the digital laminae of normal horses and horses in the developmental stages of laminitis experimentally induced by administration of black walnut extract (BWE).

Sample Population—Samples of mRNA extracted from the digital laminae of 5 control horses and 5 horses at the onset of leukopenia after administration of BWE.

Procedure—Specimens of laminae were collected from anesthetized horses prior to euthanasia. Expression of COX-1 and COX-2 mRNA in laminae of control and affected horses was evaluated via realtime quantitative polymerase chain reaction techniques.

Results—Expression of COX-2 mRNA was significantly increased in the BWE-treated group, compared with that in control horses. In contrast to COX-2 regulation, COX-1 mRNA expression was not significantly different between groups. Interestingly, despite consistent clinical signs such as leukopenia in all BWE-treated horses, distinct differences in COX-2 mRNA expression were detected among those 5 horses (compared with values for control horses, the increase in COX-2 mRNA expression ranged from no increase to a 30-fold increase).

Conclusions and Clinical Relevance—Results indicated that there was a significant upregulation of COX-2 mRNA expression during the developmental stages of laminitis, with no significant change in expression of the COX-1 isoform. These data appear to provide support for aggressive use of nonsteroidal anti-inflammatory drugs in horses at risk for laminitis; further investigation into the clinical value of selective COX-2 inhibitors for treatment of laminitis in horses appears to be warranted. (Am J Vet Res 2004;65:1724–1729)

Abstract

Objective—To compare the levels of mRNA expression of cycooxygenase (COX)-1 and COX-2 in the digital laminae of normal horses and horses in the developmental stages of laminitis experimentally induced by administration of black walnut extract (BWE).

Sample Population—Samples of mRNA extracted from the digital laminae of 5 control horses and 5 horses at the onset of leukopenia after administration of BWE.

Procedure—Specimens of laminae were collected from anesthetized horses prior to euthanasia. Expression of COX-1 and COX-2 mRNA in laminae of control and affected horses was evaluated via realtime quantitative polymerase chain reaction techniques.

Results—Expression of COX-2 mRNA was significantly increased in the BWE-treated group, compared with that in control horses. In contrast to COX-2 regulation, COX-1 mRNA expression was not significantly different between groups. Interestingly, despite consistent clinical signs such as leukopenia in all BWE-treated horses, distinct differences in COX-2 mRNA expression were detected among those 5 horses (compared with values for control horses, the increase in COX-2 mRNA expression ranged from no increase to a 30-fold increase).

Conclusions and Clinical Relevance—Results indicated that there was a significant upregulation of COX-2 mRNA expression during the developmental stages of laminitis, with no significant change in expression of the COX-1 isoform. These data appear to provide support for aggressive use of nonsteroidal anti-inflammatory drugs in horses at risk for laminitis; further investigation into the clinical value of selective COX-2 inhibitors for treatment of laminitis in horses appears to be warranted. (Am J Vet Res 2004;65:1724–1729)