Effects of tempol, a membrane-permeable radical scavenger, on the multiple organ failure induced by zymosan in the rat

Here we have investigated the effects of tempol, a membrane-permeable radical scavenger, on the multiple organ failure (MOF) caused by zymosan in the rat. Zymosan administration causes an enhanced formation of reactive oxygen species (ROS), which contribute to the pathophysiology of MOF. MOF was induced by zymosan (500 mg/kg, suspended in saline solution, i.p.). After zymosan or saline administration, animals were monitored for evaluation of mortality for 12 days. Treatment of rats with tempol (10, 30 or 100 mg/kg i.p. I and 6 hour after zymosan) attenuated the peritoneal exudation and the migration of polymorphonuclear cells (PMNs) caused by zymosan in a dose-dependent fashion. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in lung, liver and intestine from zymosan-treated rats. The degree of staining for nitrotyrosine was markedly reduced in tissue sections obtained from zymosan-treated rats, which had received tempol (100 mg/kg i.p.). This study provides the evidence that tempol, a small molecule that permeates biological membranes and scavenges ROS, attenuates the degree of MOF associated with zymosan-induced peritonitis in the rat.