Anti-inflammatory effect of ATB-352, a H2S -releasing ketoprofen derivative, on lipopolysaccharide-induced periodontitis in rats.

Abstract

Periodontal disease is the most common cause of tooth loss in humans, is an inflammatory disease initiated by oral microbial biofilm. Given the involvement of the inflammatory pathway in this type of pathology, the main pharmacological strategy for the treatment of periodontitis, is the inhibition of the inflammatory process in order to prevent tissue destruction and bone resorption, a condition associated with a painful state. To do this, the best class of drugs are Non-steroidal anti-inflammatory drugs (NSAIDs), however, the presence of side effects, especially at the gastrointestinal tract, limits their use for long-term therapy. Recently, some evidence shows that derivatives of NSAIDs capable of releasing hydrogen sulphide exhibit lower collateral effects, particularly at the gastric level. In fact, H2S is an endogenous gaseous mediator with a cytoprotective role at the gastric level. In this study, we have compared the protective effects of ketoprofen with ATB-352, a hydrogen sulfide-releasing derivative of ketoprofen, in an experimental model of periodontitis in rat. Periodontitis was induced by a single intragingival injection of 1 μl LPS (10 μg/μl), Our results show that 14 h after intragingival injection of LPS, there was a high tissue damage associated with bone resorption, and in gingivomucosal tissues there was a significant expression of NF-kb p65 and pro-inflammatory cytokine as well as a higher expression of COX-2 and iNOS, activation of the apoptotic process, and also increased levels of NGF expression, often associated with a higher nociceptive perception. Treatment with ATB-352 at the dose of 20mg\kg, was able to reduce the inflammatory process associated with intragingival LPS injection and also had a positive effect on bone resorption and tissue damage.

• Authors: Enrico Gugliandolo, Roberta Fusco, Ramona D'Amico, Angela Militi, Giacomo Oteri, John L Wallace, Rosanna Di Paola, Salvatore Cuzzocrea
• Journal: Pharmacological research (Pharmacol Res) Vol. 132 Pg. 220-231 (06 2018) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 29287688 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Interleukin-1beta
• Lipopolysaccharides
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Ketoprofen
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Cyclooxygenase 2
• Ptgs2 protein, rat
• Hydrogen Sulfide

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Bone Resorption
• Cyclooxygenase 2 (metabolism)
• Hydrogen Sulfide (administration & dosage)
• Interleukin-1beta (metabolism)
• Ketoprofen (analogs & derivatives, pharmacology, therapeutic use)
• Lipopolysaccharides
• Male
• Mouth Mucosa (drug effects, metabolism)
• NF-kappa B (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Periodontitis (chemically induced, drug therapy, metabolism)
• Rats, Sprague-Dawley
• Tumor Necrosis Factor-alpha (metabolism)