Inhibitory effects of dimethylacetyl-β-cyclodextrin on lipopolysaccharide-induced macrophage activation and endotoxin shock in mice

Hidetoshi Arima, Keiichi Motoyama, Akihiro Matsukawa, Yoji Nishimoto, Fumitoshi Hirayama, Kaneto Uekama

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 languageEnglish
Pages (from-to)1506-1517
Number of pages12
JournalBiochemical Pharmacology
Volume70
Issue number10
DOIs
Publication statusPublished - Nov 15 2005
Externally publishedYes

Keywords

  • Antagonist
  • Cyclodextrin
  • Dimethylacetyl-β-cyclodextrin
  • Lipopolysaccharide
  • Macrophages
  • Sepsis

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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