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 journalArticlepeer-review

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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