Joint inflammation increases glucosamine levels attained in synovial fluid following oral administration of glucosamine hydrochloride

Abstract

Objective: To compare synovial glucosamine levels in normal and inflamed equine joints following oral glucosamine administration and to determine whether single dose administration alters standard synovial parameters of inflammation. Methods: Eight adult horses were studied. On weeks 1 and 2, all horses received 20 mg/kg glucosamine hydrochloride by nasogastric (NG) intubation or intravenous injection. On weeks 3 and 4, 12 h after injection of both radiocarpal joints with 0.25 ng Escherichia coli lipopolysaccharide (LPS) to induce inflammation, glucosamine hydrochloride or a placebo was administered by NG intubation. Plasma samples were collected at baseline and 5, 15, 30, 60, 120, 360, 480 and 720 min after dosing. Synovial fluid (SF) samples were collected within 48 h before dosing and 1, 6 and 12 h post-dosing. Glucosamine was analyzed by Liquid Chromatography Electrospray Tandem Mass Spectrometry (LC-ESI/MS/MS). Clinicopathological evaluation of SF parameters included white blood cell (WBC) count and total protein (TP) analyses. Results: No significant differences between groups were observed in SF baseline levels of WBC and TP at any stage of the study. SF WBC and TP significantly increased following IA LPS. The mean (±SD) maximal SF glucosamine levels (422.3 ± 244.8 ng/mL) were significantly higher (>fourfold) in inflamed joints when compared to healthy joints (92.7 ± 34.9 ng/mL). Glucosamine did not have any effect on standard SF parameters of inflammation. Conclusion: Synovial inflammation leads to significantly higher synovial glucosamine concentrations compared to levels attained in healthy joints following oral administration of glucosamine hydrochloride. Whether these higher levels are translated into a therapeutic effect on the joint tissues remains to be elucidated. © 2008 Osteoarthritis Research Society International.