Influence of phenylbutazone on eicosanoid levels in equine acute inflammatory exudate.

The research article discusses a study on the effects of the drug phenylbutazone on eicosanoid levels during an inflammatory response in ponies. Through a cross-over experiment, it demonstrated that the administration of the drug significantly decreased eicosanoid levels and increased leukocyte numbers, suggesting its potential as a non-steroidal anti-inflammatory drug.

Research Methodology

• To investigate the effect of phenylbutazone(PBZ), an inflammation was artificially induced in seven ponies. This was achieved by subcutaneous implantation of three sterile sponge strips that had been soaked in carrageenan.
• A single therapeutic dose of PBZ was administered intravenously at the time of sponge implantation. PBZ dosage was 4.4 mg/kg per pony.
• The inflammatory exudates that were produced as a result of the sponge implantation were then harvested at 6, 12, and 24 hours post-implantation.
• The exudates were examined for leukocyte (white blood cell) and erythrocyte (red blood cell) numbers using the improved Neubauer technique which is a method for counting these cell types.
• Eicosanoid levels in the exudates were also measured via radioimmunoassay, a laboratory method to measure different substances in the body.
• Finally, a high performance liquid chromatography method was utilized to identify concentrations of PBZ and its principal metabolite oxyphenbutazone in the samples.

Key Findings

• The study indicated that the administration of PBZ led to a highly significant reduction in eicosanoid levels – specifically of Prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha (a stable breakdown of Prostacyclin, PGI2) – at 6 hours. These reductions were maintained at 12 and 24 hours.
• The level of Thromboxane B2 (TXB2), another eicosanoid which is the product of TXA2, was also found to be reduced in treated animals at 6 and 12 hours, although this finding was not statistically significant.
• Leukocyte numbers were significantly increased from those at 6 hours at both 12 and 24 hours in both control and PBZ-treated animals. However, the difference between control and treated animals was not significant.

Implications

• This study is the first to report the inhibition of eicosanoids in ponies following the administration of a non-steroidal anti-inflammatory drug (NSAID like PBZ).
• As such, it suggests that the inflammatory model used in this study could be a potential way of evaluating the effectiveness and longevity of NSAIDs in horses.