Abstract | OBJECTIVE: MATERIALS AND 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 | A E Dief, D K Mostafa, G M Sharara, T H Zeitoun |
Journal | European review for medical and pharmacological sciences
(Eur Rev Med Pharmacol Sci)
Vol. 19
Issue 8
Pg. 1537-46
(Apr 2015)
ISSN: 2284-0729 [Electronic] Italy |
PMID | 25967731
(Publication Type: Journal Article)
|
Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Naproxen
- Zymosan
- Hydrogen Sulfide
|
Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology, therapeutic use)
- Arthritis, Experimental
(chemically induced, prevention & control)
- Hydrogen Sulfide
(pharmacology, therapeutic use)
- Injections, Intra-Articular
- Male
- Naproxen
(pharmacology, therapeutic use)
- Neutrophils
(drug effects)
- Pain
(chemically induced, drug therapy)
- Rats
- Rats, Wistar
- Zymosan
(toxicity)
|