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 |
|---|---|
| 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 |
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Keywords
- Antagonist
- Cyclodextrin
- Dimethylacetyl-β-cyclodextrin
- Lipopolysaccharide
- Macrophages
- Sepsis
ASJC Scopus subject areas
- Pharmacology
Cite this
Inhibitory effects of dimethylacetyl-β-cyclodextrin on lipopolysaccharide-induced macrophage activation and endotoxin shock in mice. / Arima, Hidetoshi; Motoyama, Keiichi; Matsukawa, Akihiro; Nishimoto, Yoji; Hirayama, Fumitoshi; Uekama, Kaneto.
In: Biochemical Pharmacology, Vol. 70, No. 10, 15.11.2005, p. 1506-1517.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibitory effects of dimethylacetyl-β-cyclodextrin on lipopolysaccharide-induced macrophage activation and endotoxin shock in mice
AU - Arima, Hidetoshi
AU - Motoyama, Keiichi
AU - Matsukawa, Akihiro
AU - Nishimoto, Yoji
AU - Hirayama, Fumitoshi
AU - Uekama, Kaneto
PY - 2005/11/15
Y1 - 2005/11/15
N2 - 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.
AB - 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.
KW - Antagonist
KW - Cyclodextrin
KW - Dimethylacetyl-β-cyclodextrin
KW - Lipopolysaccharide
KW - Macrophages
KW - Sepsis
UR - http://www.scopus.com/inward/record.url?scp=26944480084&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=26944480084&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2005.08.021
DO - 10.1016/j.bcp.2005.08.021
M3 - Article
C2 - 16214116
AN - SCOPUS:26944480084
VL - 70
SP - 1506
EP - 1517
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 10
ER -