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

Background and Methods: We investigated the effects of tempol, a membrane-p ermeable radical scavenger, on the multiple organ failure (MOF) caused by z ymosan in the rat. Zymosan (500 mg/kg, suspended in saline solution, ip) en hances formation of reactive oxygen species, which contribute to the pathop hysiology of MOF. After zymosan or saline administration, animals were moni tored for 12 days. Results: Treatment of rats with tempol (10, 30, or 100 mg/kg ip, 1 and 6 hr s after zymosan) attenuated the peritoneal exudation and the migration of p olymorphonuclear cells caused by zymosan in a dose-dependent fashion. Tempo l also attenuated the lung, liver, and intestinal injury (histology) as wel l as the increase in the concentrations of myeloperoxidase and malondialdeh yde caused by zymosan in the lung, liver, and intestine. Immunohistochemica l analysis for nitrotyrosine and for poly(adenosine 5'-diphosphate-ribose)s ynthetase demonstrated a positive staining in lung, liver, and intestine fr om zymosan-treated rats. The degree of staining for nitrotyrosine and for p oly(adenosine 5'-diphosphate-ribose) synthetase was markedly reduced in tis sue sections obtained from zymosan-treated rats that had received tempol (1 00 mg/kg ip). Furthermore, treatment of rats with tempol significantly redu ced the following: a) the formation of peroxynitrite, b) the DNA damage, c) the impairment in mitochondrial respiration, and d) the decrease in the ce llular concentration of oxidized nicotinamide adenine dinucleotide observed in macrophages harvested from the peritoneal cavity of rats treated with z ymosan. Conclusion: This study provides the first evidence that tempol, a small mol ecule that permeates biological membranes and scavenges reactive oxygen spe cies, attenuates the degree of MOF associated with zymosan-induced peritoni tis in the rat.