title: Hydrogen sulfide releasing naproxen offers better anti-inflammatory and chondroprotective effect relative to naproxen in a rat model of zymosan induced arthritis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology; Department of Clinical Pharmacology; Department of Medical Biochemistry; 4Department of Histology and Cell Biology; Faculty of Medicine, University of Alexandria, Egypt. dalia.kashishy@alexmed.edu.eg.
authors.forename: A E
authors.initials: AE
authors.lastname: Dief
authors.forename: D K
authors.initials: DK
authors.lastname: Mostafa
authors.forename: G M
authors.initials: GM
authors.lastname: Sharara
authors.forename: T H
authors.initials: TH
authors.lastname: Zeitoun
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000139:chemically induced* / Q000517:prevention & control*; D006862:Hydrogen Sulfide / Q000494:pharmacology / Q000627:therapeutic use*; D007270:Injections, Intra-Articular; D008297:Male; D009288:Naproxen / Q000494:pharmacology / Q000627:therapeutic use*; D009504:Neutrophils / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D015054:Zymosan / Q000633:toxicity*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen; D015054:Zymosan; D006862:Hydrogen Sulfide