title: Inhibitory effect of triamcinolone acetonide on synthesis of inflammatory mediators in the equine.
abstract: Glucocorticoids (corticosteroids) are widely used anti-inflammatory agents in veterinary medical practice. These drugs are considered doping agents because they mask pain and thus, increase injury potential in equine athletes. They exhibit anti-inflammatory property by binding to glucocorticoids receptor (GR) to control the transcription of pro- and anti-inflammatory cytokines and enzymes involved in the synthesis of bioactive eicosanoids. To evaluate the role of triamcinolone acetonide (TA) on concentrations of bioactive eicosanoids in equine plasma, TA (0.04 mg/kg) was intravenously administered to horses. Before (0 h) and after TA administration, equine whole blood (EWB) samples were collected and challenged with either methanol (vehicle), calcium ionophore A-23187 (CI) or lipopolysaccharide (LPS) to stimulate ex-vivo synthesis of eicosanoids. Plasma concentrations of eicosanoids were quantified using LC-MS/MRM. Results showed that thromboxane B2 (TXB2) was not affected by TA administration when EWB was stimulated with CI. However, after LPS treatment, TXB2, PGE2, PGF2α and 15-(s)-HETE decreased during 2-8 h post-TA administration but recovered to concentrations which were not significantly different from those of pre-TA administration (0 h), after 24 h. When EWB was treated with CI, LTB4 was suppressed post-TA administration compared to 0 h. When EWB collected after TA administration was stimulated with LPS, LTB4 was not significantly different from those of 0 h. Administration of a therapeutic dose of TA (0.04 mg/kg, iv) in the horse suppressed biosynthesis of bioactive eicosanoids indicating the anti-inflammatory role of TA in the horse.
authors.affiliation: University of Pennsylvania School of Veterinary Medicine, Department of Clinical Studies, New Bolton Center Campus, 382 West Street Road, Kennett Square, PA 19348, USA.
authors.forename: Dipti
authors.initials: D
authors.lastname: Mangal
authors.affiliation: University of Pennsylvania School of Veterinary Medicine, Department of Clinical Studies, New Bolton Center Campus, 382 West Street Road, Kennett Square, PA 19348, USA; PA Equine Toxicology and Research Center, West Chester University, Department of Chemistry, 220 East Rosedale Avenue, West Chester, PA 19382, USA. Electronic address: ubohcorn@vet.upenn.edu.
authors.forename: Cornelius E
authors.initials: CE
authors.lastname: Uboh
authors.affiliation: University of Pennsylvania School of Veterinary Medicine, Department of Clinical Studies, New Bolton Center Campus, 382 West Street Road, Kennett Square, PA 19348, USA.
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Soma
authors.affiliation: University of Pennsylvania School of Veterinary Medicine, Department of Clinical Studies, New Bolton Center Campus, 382 West Street Road, Kennett Square, PA 19348, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D015777:Eicosanoids / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D005938:Glucocorticoids / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006736:Horses; D008070:Lipopolysaccharides / Q000494:pharmacology; D000432:Methanol / Q000494:pharmacology; D014222:Triamcinolone Acetonide / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D015777:Eicosanoids; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D000001:Calcimycin; D014222:Triamcinolone Acetonide; D000432:Methanol
keywords: Eicosanoids; Equine whole blood; Glucocorticoids; LC-MS/MRM; Lipopolysaccharide; Triamcinolone acetonide