PMID: 8586485Jul 1, 1995Paper

Reduction in endotoxin-induced organ dysfunction and cytokine secretion by a cyclic nitrone antioxidant

International Journal of Immunopharmacology
T R DownsJ F French

Abstract

Multiple organ dysfunction (MOD) is the leading cause of mortality in septic patients with circulatory shock. Recent evidence suggests that the overproduction of the cytokine, tumor necrosis factor-alpha(TNF), and oxygen free radical molecules may mediate the progression of sepsis to MOD and death. In this study, we have examined the ability of MDL 101,002, a free radical scavenger, to reduce organ dysfunction and cytokine secretion induced by lipopolysaccharide (LPS) administration in rats. Treatment with MDL 101,002(10-60 ng/kg, i.p.) 30 min prior to an LPS challenge resulted in a dose-dependent reduction in several markers indicative of organ dysfunction and mortality. MDL 101,002 markedly decreased LPS-induced liver and kidney damage as indicated by serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) or urea and creatinine, respectively. MDL 101,002 also prevented LPS-induced pulmonary edema, but did not prevent leukopenia and only partially reduced thrombocytopenia. Associated with these improvements in organ dysfunction and survival was a modest decrease in LPS-stimulated interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) secretion and a marked ( > 90%) inhibition of TNF se...Continue Reading

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Citations

Jan 1, 1997·Journal of Cancer Research and Clinical Oncology·V B Grossie, D Mailman
Mar 24, 2004·International Immunopharmacology·Victor M VictorMonica De la Fuente
Jan 1, 1997·Free Radical Biology & Medicine·J L DageC E Thomas
Feb 10, 2000·Critical Care Medicine·C C WinterbournJ A Windsor
Feb 9, 1996·The Journal of Biological Chemistry·C E ThomasR C Bernotas

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