Dief A E, Mostafa D K, Sharara G M, Zeitoun T H
Department of Physiology; Department of Clinical Pharmacology; Department of Medical Biochemistry; 4Department of Histology and Cell Biology; Faculty of Medicine, University of Alexandria, Egypt.
Eur Rev Med Pharmacol Sci. 2015 Apr;19(8):1537-46.
Hydrogen sulfide (H2S) is rapidly gaining ground as a physiological mediator of inflammation, but there is no clear consensus as to its precise role in inflammation. Therefore, this study was undertaken to evaluate the effects of ATB-346 as a novel H2S-releasing naproxen compared to naproxen, as a traditional non-steroidal anti-inflammatory drug on zymosan induced mono-arthritis in rats.
Male Wistar rats (n=48) were randomly assigned to four main groups: normal control, untreated arthritis, Naproxen and ATB-346 treated groups. Mono-arthritis was induced by intra-articular injection of zymosan into the knee joints. Mechanical hypernociception and joint swelling were evaluated at 6 hours and 5 days. Inflammatory cellular recruitment and adherence, tumor necrosis factor alpha, nuclear factor kappa β, total sulfide levels, and histological changes were evaluated in knee lavages, blood or joint tissues at selected time points.
Zymosan injection evoked knee inflammation and pain as characterized by mechanical hypernociception, impaired gait, joint swelling with inflammatory exudation and histological changes. Treatment with ATB-346 attenuated nociceptive responses, inflammatory cellular and biochemical changes in comparison to naproxen. Only ATB-346 was able to suppress neutrophil adherence and to preserve normal articular structure.
H2S releasing naproxen represents an advancement over the parent drug, naproxen. Apart from the superior anti-inflammatory and anti-noceiceptive activity, ATB-346 offered a distinguished chondroprotective effect and is almost devoid from naproxen deleterious effects on articular cartilage.
硫化氢（H₂S）作为一种炎症的生理介质正迅速受到关注，但关于其在炎症中的确切作用尚无明确共识。因此，本研究旨在评估新型释放H₂S的萘普生ATB - 346与传统非甾体抗炎药萘普生相比，对大鼠酵母聚糖诱导的单关节炎的影响。
雄性Wistar大鼠（n = 48）随机分为四个主要组：正常对照组、未治疗的关节炎组、萘普生治疗组和ATB - 346治疗组。通过向膝关节内注射酵母聚糖诱导单关节炎。在6小时和5天时评估机械性痛觉过敏和关节肿胀。在选定时间点对膝关节灌洗液、血液或关节组织中的炎症细胞募集与黏附、肿瘤坏死因子α、核因子κβ、总硫化物水平及组织学变化进行评估。
注射酵母聚糖诱发膝关节炎症和疼痛，表现为机械性痛觉过敏、步态受损、伴有炎性渗出的关节肿胀及组织学变化。与萘普生相比，ATB - 346治疗可减轻伤害性反应、炎症细胞及生化变化。只有ATB - 346能够抑制中性粒细胞黏附并维持正常关节结构。
释放H₂S的萘普生比母体药物萘普生有进步。除了具有更强的抗炎和抗伤害感受活性外，ATB - 346还具有显著的软骨保护作用，且几乎没有萘普生对关节软骨的有害影响。
