Objective—To determine pathophysiologic effects of phenylbutazone on the equine right dorsal colon (RDC).
Animals—12 healthy adult horses.
Procedures—A controlled crossover observational study was conducted. Clinical and serum variables, colonic inflammation (histologic grading), and measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA) and prostaglandin E2 (PGE2) concentrations, ingesta volatile fatty acid (VFA) content, and arterial blood flow in the RDC were evaluated for a 21-day period in horses administered phenylbutazone (8.8 mg/kg, PO, q 24 h) or a control substance.
Results—Data from 8 horses were analyzed. Plasma albumin concentrations decreased significantly from days 10 to 21 during phenylbutazone treatment, compared with results during the same days for the control treatment. Phenylbutazone treatment caused neutropenia (< 3.0 × 103 cells/μL). No other clinical or hematologic abnormalities were detected for phenylbutazone or control treatments. Two horses developed colitis while receiving phenylbutazone. No significant differences were detected in the RDC between phenylbutazone and control treatments for MPO activity, MDA and PGE2 concentrations, and histologic evidence of inflammation. Arterial blood flow in the RDC was significantly increased during phenylbutazone treatment, compared with values for the control treatment. Differences were identified in VFA production during phenylbutazone treatment, compared with the control treatment, with a decrease in acetic acid concentrations over time.
Conclusions and Clinical Relevance—Prolonged phenylbutazone administration caused hypoalbuminemia, neutropenia, changes in RDC arterial blood flow, and changes in VFA production. Veterinarians should monitor serum albumin concentrations and neutrophil counts and be cautious when making dosing recommendations for phenylbutazone treatment of horses.
Objective—To establish an in vivo method for matrix metalloproteinase (MMP)-2 and MMP-9 induction in horses via IV administration of lipopolysaccharide (LPS) and to evaluate the ability of doxycycline, oxytetracycline, flunixin meglumine, and pentoxifylline to inhibit equine MMP-2 and MMP-9 production.
Animals—29 adult horses of various ages and breeds and either sex.
Procedures—In part 1, horses received an IV administration of LPS (n = 5) or saline (0.9% NaCl) solution (5). Venous blood samples were collected before and at specified times for 24 hours after infusion. Plasma was harvested and analyzed for MMP-2 and MMP-9 activities via zymography. In part 2, horses received doxycycline (n = 5), oxytetracycline (5), flunixin meglumine (5), or pentoxifylline (4) before and for up to 12 hours after administration of LPS. Plasma was obtained and analyzed, and results were compared with results from the LPS-infused horses of part 1.
Results—Administration of LPS significantly increased MMP-2 and MMP-9 activities in the venous circulation of horses. All MMP inhibitors significantly decreased LPS-induced increases in MMP activities but to differing degrees. Pentoxifylline and oxytetracycline appeared to be the most effective MMP-2 and MMP-9 inhibitors, whereas doxycycline and flunixin meglumine were more effective at inhibiting MMP-2 activity than MMP-9 activity.
Conclusions and Clinical Relevance—IV administration of LPS to horses caused increased venous plasma activities of MMP-2 and MMP-9. These MMP activities were reduced by pentoxifylline and oxytetracycline, suggesting that further evaluation of these medications for treatment and prevention of MMP-associated diseases in horses is indicated.