Abstract
The potential use of hydrophilic cyclodextrins (CyDs) as an inhibitor for lipopolysaccharide (LPS) was examined. Of the five CyDs used in this study, dimethylacetyl-β-cyclodextrin (DMA7-β-CyD) had greater inhibitory activity than other CyDs against the production of nitric oxide (NO) and various proinflammatory cytokines including tumor necrosis factor-α (TNF-α) in murine macrophages stimulated with two serotypes of LPS and lipid A. The inhibitory effect of DMA7-β-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-β-CyD could be ascribed to the interaction with LPS. Simultaneous administration of DMA7-β-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-β-CyD decreased blood level of TNF-α as well as serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) in mice. In conclusion, DMA7-β-CyD may have promise as a new therapeutic agent for endotoxin shock induced by LPS.
Original language | English |
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Pages (from-to) | 1506-1517 |
Number of pages | 12 |
Journal | Biochemical Pharmacology |
Volume | 70 |
Issue number | 10 |
DOIs | |
Publication status | Published - Nov 15 2005 |
Externally published | Yes |
Keywords
- Antagonist
- Cyclodextrin
- Dimethylacetyl-β-cyclodextrin
- Lipopolysaccharide
- Macrophages
- Sepsis
ASJC Scopus subject areas
- Biochemistry
- Pharmacology