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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/2276

Title: Effect of fluconazole on phagocytic response of polymorphonuclear leukocytes in a rat model of acute sepsis
Authors: Khan, Haseeb Ahmad
Keywords: Effect of Fluconazole
Phagocytic Response
Polymorphonuclear
Leukocytes
Rat Model
Acute Sepsis
Issue Date: 16-Nov-2004
Publisher: Hindawi Publishing Corporation
Citation: Mediators of Inflammation: 1; 9–15
Abstract: Recently, fluconazole (FLZ) has been shown to improve survival and reduce multiorgan failure in experimental and clinical septic shock. The mechanism by which FLZ affords protection against sepsis remains obscure. This study examines the effect of FLZ on phagocytic activity of polymorphonuclear leukocytes (PMNs) in a rat model of septic shock by inducing fecal peritonitis in male Wistar rats using intraperitoneal instillation (1mL/kg) of fecal suspension in saline (1 : 1 w/v). Sham control rats received sterile fecal suspension and vehicle treatment. FLZ was administered in the doses of 0, 3, 10, and 30mg/kg by gavage 30 minutes before fecal instillation. The samples of peritoneal fluid were collected 8 hours following fecal inoculation for the evaluation of phagocytic response of PMNs using zymosan-induced luminol-dependent chemiluminescence (CL). Fecal peritonitis caused massive infiltration of PMNs in the peritoneal cavity (ANOVA F4,45 = 6.322, P < .001). Although FLZ reduced the infiltration of PMNs, this effect was neither significant nor dose dependent. The actual CL response was significantly higher in the peritoneal fluid of rats subjected to peritonitis, which was significantly and dose-dependently attenuated by FLZ treatment (ANOVA F4,45 = 11.048, P < .001). Normalization of CL response for 1000 PMNs revealed that FLZ dose-dependently albeit insignificantly reduced the activity of PMNs. The high dose of FLZ caused 2.29-fold decrement in the area under curve (AUC) pertaining to cumulative CL response. The findings of this study suggest that FLZ protects rats against septic shock by inhibiting PMN-mediated inflammatory cascade without compromising their phagocytic activity.
URI: http://hdl.handle.net/123456789/2276
Appears in Collections:College of Science

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