Alterations in the functions of the reticuloendothelial and protease-antiprotease systems after intraperitoneal injection of zymosan in rats.

Abstract

To evaluate alterations in the function of the reticuloendothelial system (RES) and potential protective effects of pretreatment with the antioxidants: N-acetyl-L-cysteine (NAC) or dimethyl sulphoxide (DMSO), after intraperitoneal injection of zymosan (0.50 mg/g body weight) in rats. Experimental study. University hospital, Sweden. 81 male Sprague-Dawley rats. Intraperitoneal injection of either 4 ml saline or zymosan suspension (0.50 mg/g body weight). One hour before the intraperitoneal injection, 1 ml of saline, or a solution of NAC (150 mg/kg) or DMSO (80 mg/kg) were given intravenously. Systemic arterial pressure, packed cell volume, concentrations of plasma proteins and plasma protease inhibitors, uptake of 125I-labelled Escherichia coli in organs, blood clearance and body uptake rate of radiolabelled E. coli, and blood flow in organs at 3, 6, and 12 hours after injection. The uptake of radiolabelled E. coli in the liver, spleen and lungs decreased significantly from 3 hours onwards after zymosan challenge (p <(0.05). Blood clearance and body uptake rate also decreased significantly from 3 hours onwards (p < 0.05), but this did not correlate with the reduction in organ blood flow. Significant falls in plasma concentrations of prekallikrein (p < 0.01) and protease inhibitors (p <0.05) suggested possible contact-phase activation and activation of the kallikrein-kinin and fibrinolytic system. Pretreatment with NAC, and to a less extent DMSO, significantly prevented these alterations in RES function. Zymosan induced an impairment in RES function that was not initially associated with a reduction in blood flow. Plasma proteolytic activity seems to be involved in the impaired RES function. Pretreatment with NAC or DMSO effectively improved RES function.