Aseptic Peritonitis Model for Drug Discovery (As Therapy)

Abstract

Peritonitis is defined as an inflammation of the serosal membrane that lines the abdominal cavity and the organs contained therein. The peritoneum, which is an otherwise sterile environment, reacts to various pathologic stimuli with a fairly uniform inflammatory response. Depending on the underlying pathology, the resultant peritonitis may be infectious or sterile (i.e., chemical or mechanical). The pathophysiology of peritonitis is complicated and is involved in various processes, of which, the most important one is the inflammatory reaction. During the pathological process of the peritonitis, NF-κB plays an activating role in the inflammatory reaction, which might be a potential therapeutic target in the future clinical work. The aim of the study was to test the anti-inflammatory and proregenerative actions of fisetin, a flavonol found in many plants, in a mouse model of thioglycollate-induced peritonitis as well as the actions of fisetin administered with a nanoparticle such as mesoporous carbon nanoparticle (MCN). BALB/c mice were used in this study. We found cell recruitment in the blood increases with the administration of TG after 24, 48, and 96 h, showing that it has induced inflammation. Cell recruitment is successfully inhibited by fisetin after 24 h (p < 0.05), and with MCN + fisetin after 48 h (p < 0.05). In the peritoneal fluid, total cell recruitment has increased after 24 h (p < 0.05), which is successfully inhibited with fisetin treatment after 96 h. TG treatment has significantly reduced cell proliferation in the blood, PF and BM, within 24 h, till 96 h. Interestingly, cell proliferation has increased with fisetin treatment after 24 h, and with MCN + fisetin after 24 h (in PF) and after 48 h (in PB and BM). The clonogenic potential of the tissues decreases significantly within 24 h, with administration of TG. Both fisetin treatment and MCN + fisetin treatment have restored the clonogenic potential of the tissues after 24 h. There was a decrease in Th2 cytokines with TG treatment, in blood after 48 h and fisetin and MCN + fisetin has increased the cytokine content. In conclusion, we found that fisetin had a promising therapeutic effect on the peritonitis.

Therapeutic use of fisetin and fisetin loaded on mesoporous carbon nanoparticle (MCN) in thioglycollate-induced peritonitis.