ArticleMedical gas research2013
A comparative study on the anti-inflammatory effects of single oral doses of naproxen and its hydrogen sulfide (H2S)-releasing derivative ATB-346 in rats with carrageenan-induced synovitis.
Article in Medical gas research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 49 citations in OpenAlex.
- Preclinical Evaluation of a Nanoformulated Hydrogen Sulfide-releasing Dexamethasone for Topical Treatment of Psoriasis.Pharmaceutical research · 2026Article
- Prenatal Naproxen Reprograms Histopathological and Molecular Facets of the Sex-Based Lung Injury in Adult Offspring of Preeclamptic Rats.International journal of molecular sciences · 2026Article
- Beneficial Effects of Two Hydrogen Sulfide (HPharmaceutics · 2023Article
- Article
- The Role of Hydrogen Sulfide in Respiratory Diseases.Biomolecules · 2021Review
- Hydrogen Sulfide and the Immune System.Advances in experimental medicine and biology · 2021Article
- Gaseous Mediators as a Key Molecular Targets for the Development of Gastrointestinal-Safe Anti-Inflammatory Pharmacology.Frontiers in pharmacology · 2021Review
- Intraarticular Administration Effect of Hydrogen Sulfide on an In Vivo Rat Model of Osteoarthritis.International journal of molecular sciences · 2020Article
- Hydrogen Sulfide as Potential RegulatoryInternational journal of molecular sciences · 2020Review
- Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols.Frontiers in pharmacology · 2020Review
- The HFrontiers in pharmacology · 2019Article
- The dichotomous role of HBiochemical pharmacology · 2018Review
- International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of HPharmacological reviews · 2017Review
- D-Penicillamine modulates hydrogen sulfide (H2S) pathway through selective inhibition of cystathionine-γ-lyase.British journal of pharmacology · 2016Article
- The H2S-releasing naproxen derivative, ATB-346, inhibits alveolar bone loss and inflammation in rats with ligature-induced periodontitis.Medical gas research · 2015Article
- Hydrogen sulfide, a potential novel drug, attenuates concanavalin A-induced hepatitis.Drug design, development and therapy · 2014Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNon-steroidal antiinflammatory drugs (NSAIDs) are the most commonly prescribed agents for arthritic patients, although gastric effects limit their long-term use. Considering the reported gastric safety of hydrogen sulfide (H2S)-releasing NSAIDs, in addition to the anti-inflammatory effects of H2S administration to rats with synovitis, we decided to evaluate the effects of the H2S-releasing naproxen derivative ATB-346 in this animal model.
methodsMale Wistar rats were anesthetized with inhalatory halothane and pre-treated with equimolar oral doses of either naproxen (0.3, 1, 3 or 10 mg/kg) or ATB-346 (0.48, 1.6, 4.8, or 16 mg/kg) 30 min before the i.art. injection of 7.5 mg of carrageenan (CGN) into the right knee joint cavity. Joint swelling and pain score were assessed after 1, 3 and 5 h, and tactile allodynia after 2 and 4 h. After the last measurement, the joint cavity lavages were performed for counting of the recruited leukocytes. The drugs (at the highest doses) were also tested for their gastric effects by evaluating macroscopical damage score and neutrophil recruitment (measured as myeloperoxidase - MPO activity) in the stomachs 5 h after administration of the drugs. In addition, the serum naproxen pharmacokinetic profiles of both compounds, administered at the highest equimolar doses, were obtained during the first 6 h after dosing.
resultsAt the two highest tested doses, both naproxen and ATB-346 reduced edema and pain score (measured 3 and 5 h after CGN; P < 0.001). Tactile allodynia was similarly inhibited by ~45% 4 h after CGN by both naproxen (at 1, 3 and 10 mg/kg) and ATB-346 (at 1.6 and 4.8 mg/kg; P < 0.001), as well as leukocyte infiltration. Naproxen (but not ATB-346) induced significant gastric damage and, despite the increased gastric MPO activity by ~130% in the naproxen-, but not in the ATB-346-treated rats, this effect was of no statistical significance.
conclusionThe presence of a H2S-releasing moiety in the ATB-346 structure does not impair the antiinflammatory activity of the parent compound in rats with CGN-induced synovitis. In addition, released H2S may account for the absence of deleterious gastric effects, thus making of ATB-346 a potentially useful therapeutic alternative to traditional naproxen for treatment of patients with arthritis.
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