SAT0056 Osteoarthritis severity is reduced by intra-articular administration of hydrogen sulfide

• Published in: Annals of the rheumatic diseases Vol. 77; no. Suppl 2; p. 892
• Main Authors: Burguera, E.F., Vela-Anero, Á., Hermida-Gómez, T., Filgueira-Fernández, P., Gato-Calvo, L., Meijide-Failde, R., Blanco, F.J.
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2018
• Subjects: Arthritis; Cartilage (articular); Cartilage diseases; Clinical trials; Femur; Hydrogen; Hydrogen sulfide; Injection; Knee; Long-term effects; Meniscus; Osteoarthritis; Pain; Salts; Supplements; Surgery; Synovium
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2018-eular.3635

BackgroundOsteoarthritis (OA) is a chronic inflammatory disease leading to cartilage loss and eventual joint destruction. Exogenous supplementation of hydrogen sulphide (H2H) with synthetic salts in in vitro models of OA has been shown to exert anti-inflammatory effects and to result in reduced cartilage degradation1 ObjectivesTo evaluate the effects of administering an H2S-producing compound intra-articularly in an experimental model of OA.MethodsExperimental OA was induced in Wistar rats by transecting the medial collateral ligament and removing the medial meniscus of the left knee. Right knees were used as control. Animals were randomised into 3 groups (3 rats per group). Group 1 (intra-articular sulphide, IS): A single intra-articular injection of GYY4137 (200 mM in saline, 50 ml) at day 7. Group 2 (intra-articular control, IC): A single intra-articularly injection of vehicle (saline, 50 ml) at day 7. Group 3 (Surgical control, C): No treatment.Gross evaluation of the animals at days 0 (before surgery), 7, 15 and 40 (euthanasia) included indirect evaluation of pain in a Rotarod performance test. Histopathological changes in articular cartilage and synovium were evaluated with the Mankin Score (MS) and the Krenn Score (KS), respectively.ResultsAll 3 groups showed worse performance in the Rotarod test at day 7 after surgery. Number of falls was significantly increased (except in IC) and time to 1 st fall was reduced (table 1). At day 40, there was no significant improvement in either of these parameters in group C, while in IC the n# of falls had returned to pre-surgical levels. In IS there were significant improvements with respect to day 0 and both C and IC groups (table 1). Times to 1 st fall were also significantly better in the IS group vs. C and IC both at days 15 and 40.Histology showed no significant differences among groups in the lateral tibial plateau (TP) or femoral condyle (FC) separately or in the compartment as a whole. Conversely, MS in the medial compartment were significantly better in the IS group vs the C group, both when considering TP or FC separately, and for the whole compartment (figure 1). No significant differences were found among groups on the Krenn Scores.Abstract SAT0056 – Table 1Number of falls (n±sd) and time to first fall (s) in a Rotarod. C: control group; IC: intra-articular control; IS: intra-articular sulphide (n=3/group). #p<0.05 vs. T0; *p<0.05 vs. C. $p<0.05 vs. IC.Falls (n±sd)Time to 1 st fall (s) T0T7T15T40T0T7T15T40 C0.8±0.74.0±0.9#4.0±0.9#3.7±1.7#233.7±77.857.2±35.2#90.3±67.5#77.8±40.2#IC1.7±1.03.3±1.72.2±1.o2.0±0.9209.2±78.231.7±11.7#90.8±20.9#143.3±50.3IS1.3±0.84.0±1.5#2.5±1.10.0±0.0#*$265.3±58.878.5±65.9#196.3±81.3*$300.0±0.0*$ConclusionsExogenous H2S administered intra-articularly (200 mM GYY4137 in 50 ml saline) can reduce the severity of cartilage destruction in an in vivo model of OA as compared to no treatment or a vehicle control. H2S also led to a reduction in pain levels as demonstrated by a performance test. Therefore, hydrogen sulphide is a viable pharmacological candidate for OA treatment and should be further tested, including human clinical trials.Reference[1] Vela-Anero A, et al. Long-term effects of hydrogen sulfide on the anabolic-catabolic balance of articular cartilage in vitro. Nitric Oxide2017;70:42–50.Disclosure of InterestNone declared