Plasma matrix metalloproteinase activity in horses after intravenous infusion of lipopolysaccharide and treatment with matrix metalloproteinase inhibitors.
Abstract: 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. Methods: 29 adult horses of various ages and breeds and either sex. Methods: 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: 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.
Publication Date: 2013-02-27 PubMed ID: 23438126DOI: 10.2460/ajvr.74.3.473Google Scholar: Lookup
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- Journal Article
Summary
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The research involved investigating a method for inducing matrix metalloproteinase in horses through an intravenous administration of lipopolysaccharide (LPS). The study also assessed the capacity of four known matrix metalloproteinase inhibitors to restrain the production of MMP-2 and MMP-9 in horses.
Objective and Methodology
- The research aimed to create an in vivo method to induce matrix metalloproteinase-2 (MMP-2) and MMP-9 in horses using an intravenous (IV) administration of lipopolysaccharide (LPS).
- Further, the study evaluated the effectiveness of doxycycline, oxytetracycline, flunixin meglumine, and pentoxifylline as MMP-2 and MMP-9 inhibitors.
- The study was divided in two parts. In the first part, LPS or saline solution was administered to five horses intravenously and blood samples collected at specific intervals for 24 hours subsequent to the infusion. The samples were analysed for MMP-2 and MMP-9 activities.
- In the second part, the four inhibitors were administered to the horses before and up to 12 hours after the administration of LPS. The resulting plasma was again analyzed and compared with the LPS-infused horses from part one of the study.
Results
- The results showed the intravenous administration of LPS significantly increased the activities of MMP-2 and MMP-9 in the horses’ venous circulation.
- All four MMP inhibitors significantly decreased the LPS-induced increase in MMP activities, though to varying extents.
- Pentoxifylline and oxytetracycline emerged as the most effective inhibitors of both MMP-2 and MMP-9, while doxycycline and flunixin meglumine showed a higher propensity for inhibiting MMP-2 activity over MMP-9 activity.
Conclusion
- The study concluded that the intravenous administration of LPS to horses results in increased venous plasma activities of MMP-2 and MMP-9.
- The activity of these MMPs was effectively reduced by pentoxifylline and oxytetracycline, indicating the potential use of these medications in the treatment and prevention of MMP-associated diseases in horses.
Cite This Article
APA
Fugler LA, Eades SC, Moore RM, Koch CE, Keowen ML.
(2013).
Plasma matrix metalloproteinase activity in horses after intravenous infusion of lipopolysaccharide and treatment with matrix metalloproteinase inhibitors.
Am J Vet Res, 74(3), 473-480.
https://doi.org/10.2460/ajvr.74.3.473 Publication
Researcher Affiliations
- Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. lfugler@tigers.lsu.edu
MeSH Terms
- Animals
- Body Temperature / drug effects
- Clonixin / analogs & derivatives
- Clonixin / pharmacology
- Doxycycline / pharmacology
- Endotoxemia / enzymology
- Endotoxemia / veterinary
- Enzyme Induction / drug effects
- Enzyme Inhibitors / pharmacology
- Female
- Heart Rate / drug effects
- Horses / blood
- Lipopolysaccharides / pharmacology
- Male
- Matrix Metalloproteinase 2 / biosynthesis
- Matrix Metalloproteinase 2 / blood
- Matrix Metalloproteinase 9 / biosynthesis
- Matrix Metalloproteinase 9 / blood
- Oxytetracycline / pharmacology
- Pentoxifylline / pharmacology
- Random Allocation
- Respiratory Rate / drug effects
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