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Louisiana State University

1. Fugler, Lee Ann. Matrix metalloproteinases in the equine systemic inflammatory response: implications for equine laminitis.

Degree: PhD, Veterinary Medicine, 2008, Louisiana State University

Laminitis is a crippling and often life-threatening disease of the equine foot. Soft tissue damage characteristic of this disease has been associated with increased MMP activity. Therefore, it seems likely that MMPIs could be potential therapeutic agents for laminitis. Further characterization of equine MMPs and evaluation of the effectiveness of MMPIs in the horse are needed. Equine MMP-9 was harvested from neutrophils, purified by affinity chromatography, and evaluated using western blotting and gelatin zymography. The Biotrak MMP-9 Activity Assay was evaluated for use with equine samples using equine neutrophil MMP-9 as a standard, and was determined to have insufficient sensitivity for equine MMP-9. Therefore, zymography was used for evaluating MMP activity in all studies. The abilities of doxycycline, oxytetracycline, and flunixin meglumine to inhibit LPS-induced equine MMP-2 and MMP-9 activities in vitro were investigated using a digital laminar explant model. The structural integrity of the explants was tested using an Instron biomechanical testing device, and MMP activity in the explants medium was evaluated using zymography. Doxycycline, oxytetracycline, and flunixin meglumine all successfully inhibited equine MMP-9 to varying degrees. However, only doxycycline and oxytetracycline increased the structural integrity of the explants. Explant structural integrity was inversely correlated with MMP-2 concentrations in the medium. Based on the in vitro results, a non-terminal in vivo model for investigating MMPIs in the horse was validated. The administration of IV endotoxin to normal adult horses resulted in significant increases in MMP-2 and MMP-9 activities, as assessed by zymography. This in vivo model of MMP induction was used to determine the effects of doxycycline, oxytetracycline, flunixin meglumine, and pentoxifylline on equine MMP inhibition. Pentoxifylline and oxytetracycline appeared to be potent MMP-9 and modest MMP-2 inhibitors in the horse. Flunixin meglumine and doxycycline were potent inhibitors of equine MMP-2, but only weak inhibitors of equine MMP-9. These findings warrant the evaluation of pentoxifylline and oxytetracycline as MMPIs in the prevention/treatment of equine laminitis.

Subjects/Keywords: equine; horse; matrix metalloproteinase; MMP; endotoxin; laminitis; doxycycline; pentoxifylline; oxytetracycline; flunixin meglumine; MMP inhibition; endotoxemia; experimental endotoxemia; systemic inflammatory response; SIRS; laminae; laminar explants; biomechanical testing; zymography

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APA (6th Edition):

Fugler, L. A. (2008). Matrix metalloproteinases in the equine systemic inflammatory response: implications for equine laminitis. (Doctoral Dissertation). Louisiana State University. Retrieved from etd-01212009-182854 ; https://digitalcommons.lsu.edu/gradschool_dissertations/908

Chicago Manual of Style (16th Edition):

Fugler, Lee Ann. “Matrix metalloproteinases in the equine systemic inflammatory response: implications for equine laminitis.” 2008. Doctoral Dissertation, Louisiana State University. Accessed January 22, 2021. etd-01212009-182854 ; https://digitalcommons.lsu.edu/gradschool_dissertations/908.

MLA Handbook (7th Edition):

Fugler, Lee Ann. “Matrix metalloproteinases in the equine systemic inflammatory response: implications for equine laminitis.” 2008. Web. 22 Jan 2021.

Vancouver:

Fugler LA. Matrix metalloproteinases in the equine systemic inflammatory response: implications for equine laminitis. [Internet] [Doctoral dissertation]. Louisiana State University; 2008. [cited 2021 Jan 22]. Available from: etd-01212009-182854 ; https://digitalcommons.lsu.edu/gradschool_dissertations/908.

Council of Science Editors:

Fugler LA. Matrix metalloproteinases in the equine systemic inflammatory response: implications for equine laminitis. [Doctoral Dissertation]. Louisiana State University; 2008. Available from: etd-01212009-182854 ; https://digitalcommons.lsu.edu/gradschool_dissertations/908

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