betadex and Shock--Septic

The potential use of hydrophilic cyclodextrins (CyDs) as an inhibitor for lipopolysaccharide (LPS) was examined. Of the five CyDs used in this study, dimethylacetyl-beta-cyclodextrin (DMA7-beta-CyD) had greater inhibitory activity than other CyDs against the production of nitric oxide (NO) and various proinflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) in murine macrophages stimulated with two serotypes of LPS and lipid A. The inhibitory effect of DMA7-beta-CyD on NO production was also observed in macrophages stimulated with lipoteichoic acid (LTA), but not peptidoglycan (PGN), polyinosinic-polycytidylic acid (poly I:C) or CpG oligonucleotide (CpG-ODN). Several studies have suggested that the inhibitory effects of DMA7-beta-CyD could be ascribed to the interaction with LPS. Simultaneous administration of DMA7-beta-CyD not only intraperitoneally but also intravenously and intraperitoneal injection of aqueous solution containing LPS and d-galactosamine in murine endotoxin shock model suppressed fatality. Also, DMA7-beta-CyD decreased blood level of TNF-alpha as well as serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) in mice. In conclusion, DMA7-beta-CyD may have promise as a new therapeutic agent for endotoxin shock induced by LPS.

Topics: Animals; Aspartate Aminotransferases; beta-Cyclodextrins; Cell Line; Cell Nucleus; Cell Survival; Cyclodextrins; Drug Interactions; Galactosamine; Ligands; Lipopolysaccharides; Macrophage Activation; Macrophage Inflammatory Proteins; Mice; NF-kappa B; Nitric Oxide; Shock, Septic; Toll-Like Receptors; Tumor Necrosis Factor-alpha