Prophylactic Use of Fisetin in Thioglycollate-Induced Peritonitis in Mice

Infectious or non-infectious peritonitis leads to systemic inflammation due to violation of the peritoneum which is often fatal. Fisetin, a flavonol compound, exhibits a broad spectrum of biological activities including anti-oxidant, anti-inflammatory, anti-cancer and neuro-protective effects. It was used in a murine model of thioglycollate (TG)induced aseptic peritonitis to investigate its antiinflammatory effects, and on RAW macrophage cells. In this study, peritonitis was induced in C57BL/6J mice using thioglycollate, and anti-inflammatory effects of fisetin, was assessed prophylactically. In in vitro study, cells treated with inflammatory agents like bacterial lipopolysaccharide (LPS) and phorbol-12-myristate-13-acetate (PMA) lose their viability and proliferative capacity. Fisetin has been shown to prevent the loss of viability when given prophylactically. In in vivo model, total cell recruitment was found to increase with TG, showing that it has induced inflammation. Interestingly cell recruitment was successfully inhibited by fisetin. The differential count of peripheral blood, treated only with TG, shows an increase in the polymorpho-nuclear (PMN) cell count, as compared to control. On treatment with Fisetin, PMN number decreases. Concentration of nitric oxide (NO) in intestine has increased 1.90 fold after 3 hours (p<0.05) and 1.24 fold after 24 hours (p<0.05), after treatment with TG as compared to control. NO concentration has decreased 1.28 fold after 3 hours (p<0.05) and 2.15 fold after 24 hours (p<0.05) with fisetin treatment, compared to only TG. Concentration of ascorbic acid in peritoneal fluid has increased 1.06 fold after 3 hours, 1.02 fold after 9 hours and 1.05 fold after 24 hours, on treatment with only TG, as compared to control. The ascorbic acid (ASA) concentration increases significantly (p<0.05) after treatment with fisetin, compared to only TG, after 3 hours (1.38 fold), 9 hours (1.44 fold) and 24 hours (2.19 fold). In conclusion, we found that fisetin had a positive prophylactic effect against peritonitis in mice. *Corresponding author: Ena Ray Banerjee, Associate Professor, Immunology and Regenerative Medicine Research Laboratory, University of Calcutta, 35, Ballygunge Circular Road, Kolkata700019, West Bengal, India, Tel: 9163739975; Fax: 91-33-24614849; E-mail: [email protected] Received May 21, 2015; Accepted September 21, 2015; Published September 29, 2014 Citation: Mitra S, Mukherjee K, Biswas S, Banerjee ER (2015) Prophylactic Use of Fisetin in Thioglycollate-Induced Peritonitis in Mice. Biol Syst Open Access 4: 144. doi:10.4172/2329-6577.1000144 Copyright: © 2015 Mitra S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. various processes, of which, the most important one is the inflammatory reaction [3]. The pathophysiology of peritonitis is not guided by any one particular mediator, signal or pathway. The main effects of peritonitis are dysregulated coagulation systems, abnormal production of mediators, inflammatory response (which may be heightened or suppressed, depending on the type of infection), and cellular irregularities (like lymphocyte apoptosis and neutrophil hyperactivity) [3]. Inflammation leads to increased production of reactive species like ROS (reactive oxygen species), NOS (nitric oxide synthase) and their product peroxynitrite by activated macrophages. This increase in oxidative stress leads to decrease in effectiveness of oxidant defences, that is, reduction in antioxidants. Local intra-abdominal focus of inflammation caused by the microorganisms can promote the synthesis and secretion of massive inflammatory cytokines, which would destroy the endothelial junctions and provide access for bacteria into the systemic circulation leading to lethal bacteremia [4-6]. During the pathological process of the peritonitis, NF-κB plays an activating role in the inflammatory reaction [6]. Acute peritonitis is one of the most headachy postoperative complications, which is an important cause of death in surgical practice and intensive care units [7]. Acute peritonitis differs from other infections because of the broad variety of causes, severity of the infection, polymicrobial pathogenesis and complex pathological process [8].