Evaluation of intraperitoneal etanercept administration on oxidative stress parameters in rats with experimental peritonitis

Introduction: Peritonitis is an inflammation which involves visceral and/or parietal peritoneum. Without a proper treatment, peritonitis may cause a systemic inflammatory response and sepsis. Sepsis is a serious situation which has high morbidity and mortality. Cytokines trigger benefical inflammatory response to activate local coagulation to limit tissue damage in sepsis which characterized by production of proinflammatory cytokines such as TNF-α, IL – 1. However excessive production of proinflammatory cytokines break the layout of the normal immune response and constitutes inflammatory disorder of the immune response. Generally, excessive production of cytokines in sepsis results capillary leak, tissue damage and multiorgan failure is well known. Etanercept is an agent which blocks the TNF-α's binding to its cellular surface receptors as a competitive inhibitor and inhibits its biological activity. Oxidative stress is a parameter indicating tissue damage as a result of deterioration of the balance between antioxidant defense and oxidant production for any reason. Aim: to evaluate effects of etanercept administration on oxidative stress parameters in rats with induced peritonitis and to see effects on tissue injury and to investigate availability of etanercept in peritonitis in future. Matherials and Methods: In the study 28 adult female Wistar Albino rats which weights 200 - 250 grams were divided into 4 groups consisting 7 rats in each group. Experiment Groups: Control Group (Any injection of a substance was made), Peritonitis group (1,5 ml suspension of E.Coli (107 CFU/ml) was injected intraperitoneal in order to create experimental peritonitis), peritonitis + cefazolin sodium group (1 hour after injection of E.Coli for experimental peritonitis, 50mg/kg dose of cefazolin sodium was injected intraperitoneally), Peritonitis + cefazolin sodium + etanercept group (1 hour after injection of E.Coli for experimental peritonitis, 50mg/kg dose of cefazolin sodium was injected intraperitoneally. 8mg/kg/dose etanercept was injected intraperitoneal to rats with experimental peritonitis after 1 hour and 4 hours after injection of E.Coli for experimental peritonitis). 24 hours after etanercept injection experiement was ended. Peritoneal tissue samples and blood samples were taken from all groups of rats for histopathological and biochemical examinations. As oxidative stress parameters in blood and tissues: paraoxonase (PON), malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (TAC), total oxidant stress (TOS), TNF-α were studied. Results: Peritonitis group compared to the control group, oxidative parameters of serum and tissue were increased, antioxidative parameters were decreased in peritonitis group. after cefazolin injections to rats with peritonitis, reduction in oxidative parameters and increase in antioxidative parameters were observed. sefazolin + etanercept group results were more positive than the group given only cefazolin, oxidative parameters were decreased and antioxidative parameters were increased in cefazolin + etanercept group according to the cefazolin group. Histopathological changes; there was no changes in the study of section of control group peritoneal epithelium and lamina propria. In the section of peritonitis group epithelial shedding, widely neutrophil infiltration in the lamina propria, edema and capillary vascular congestion was viewed. İn the cefazolin group lesions was observed to decrease according to the peritonitis group. İn the cefazolin + etanercept group, dissappearence of epithelial desquamation, decrease of neutrophil infiltration and decrease of the severity of the edema in the lamina propria was remarkable. Conclusion: As a result of our research, we found that etanercept treatment in addition to antibiotic treatment in peritonitis gave more positive results than treatment with antibiotics alone. In accordance with these results, we consider that etanercept reduces the progression to sepsis by supression of inflammation. However more comprehensive animal experiements and human studies are needed for availability of Etanercept in treatment of pertonitis. Keywords: Experimental peritonitis, Etanercept, Oxidative stress