Linked Life Data

12628513

Source:http://linkedlifedata.com/resource/pubmed/id/12628513

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2003-3-11
pubmed:abstractText
In contrast to chemopreventive strategies using individual agents, a combination of specified compounds may be effectual to achieve desirable results with higher efficacy and lower toxicity. In the present in vitro study, we examined combinations of agents and assessed which concentrations were appropriate to yield notable synergism. L-N(G)-Monomethyl-L-arginine (L-NMMA), a synthetic inducible nitric oxide synthase (iNOS) inhibitor, and zerumbone, a natural sesquiterpene that suppresses iNOS de novo synthesis, were combined at various concentrations, with the aim to diminish combined lipopolysaccharide- and interferon-gamma-induced nitric oxide generation in a murine macrophage line, RAW264.7. Although the combinatorial effects (CEs) were antagonistic or additive at higher concentrations, significant synergism was obtained at lower concentrations where each agent alone did not cause significant inhibition. Similarly, the CEs were synergistic when (-)-epigallocatechin gallate (EGCG) and genistein were combined at lower concentrations, whereas those of two iNOS inhibitors, L-NMMA and L-N(G)-aminoethyl-L-ornithine, were either additive or antagonistic at all concentrations tested, suggesting that a combination of given agents with different action mechanisms is a prerequisite for synergistic effects. For suppression of phorbol ester-induced superoxide anion radical (O(2)*(-)) generation in differentiated HL-60 cells, the CEs of 1'-acetoxycahvicol acetate (ACA), a phenyl propanoid that suppresses O(2)*(-) generation, and O(2)*(-) dismutase were also synergistic, though only at lower concentrations. The CEs of ACA/EGCG were antagonistic or additive, even at low concentrations, suggesting that the signal transduction pathways triggered by these agents are antagonistic. The present findings suggest that individual food phytochemicals have complex interactions that can be antagonistic, additive, and/or synergistic in biological systems, depending upon certain environmental factors including concentrations. Further, these results support and emphasize the concept that combinations of different types of chemicals at low concentrations are one of the essential areas of study for chemopreventive strategies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0027-5107
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Elsevier Science B.V.
pubmed:issnType
Print
pubmed:volume
523-524
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
151-61
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:articleTitle
Synergistic suppression of superoxide and nitric oxide generation from inflammatory cells by combined food factors.
pubmed:affiliation
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan. canccer@kais.kyoto-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't