Honors College Thesis

 

Evaluation of firocoxib inhibition of cyclooxygenase activity in alpacas Public Deposited

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  • Non-steroidal anti-inflammatory drugs (NSAIDs) are used to control pain and inflammation, but can have serious adverse effects, including gastrointestinal ulceration. Non-selective NSAIDs inhibit both cyclooxygenase isoforms: COX-1 and COX-2. COX-2 is primarily responsible for the inflammatory response, while COX-1 is constitutively expressed, representing the dominant source of prostaglandins for gastric epithelial cytoprotection. The coxib class of drugs selectively reduces the activity of COX-2 while sparing protective effects of COX-1 activity. Our goal is to determine a safe and therapeutic dose of firocoxib in alpacas. There is no established method for measuring inhibition of COX-1 and COX-2 activity in alpacas. It was our aim to validate quantification of clot-induced production of thromboxane B2 (TXB₂ ) as a measure for COX-1 activity, and lipopolysaccharide-induced prostaglandin E₂ (PGE₂ ) to assess COX-2 activity and to determine how firocoxib impacts COX activity. Concentrations of TXB2 or its metabolite, 11-dehydrothromboxane B2 were not different between alpaca plasma and serum with or without acetone or methanol purification, indicating inability of the utilized ELISA to quantitate TXB2 or its metabolite in alpacas. PGE₂ increased with lipopolysaccharide exposure and 100 pg/ml firocoxib inhibited PGE₂ production by at least 80% in all animals tested, demonstrating firocoxib’s therapeutic potential in alpacas. Key Words: alpaca, firocoxib, NSAID, cyclooxygenase, camelid, prostaglandin, thromboxane
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