Linked Life Data

14568954

Source:http://linkedlifedata.com/resource/pubmed/id/14568954

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-10-21
pubmed:abstractText
We recently reported the synthesis and anti-inflammatory properties of a novel long chain polyunsaturated fatty acid (PUFA) with an oxygen atom in the beta-position, beta-oxa-21:3 n-3 (Z,Z,Z)-(octadeca-9,12,15-trienyloxy) acetic acid). Our data, from studies aimed at elucidating the mechanism of its action, show that pretreatment of human neutrophils with the beta-oxa-PUFA substantially depresses the production of leukotriene B(4) (LTB(4)) in response to calcium ionophore, A23187, comparable to standard leukotriene inhibitors such as zileuton and nordihydroguaiaretic acid. Interestingly, the n-6 equivalent, beta-oxa 21:3 n-6, is also a strong inhibitor of LTB(4) production. In contrast, naturally occurring PUFA only slightly reduce, for eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids, or increase, for arachidonic acid (20:4n-6), the formation of LTB(4). The parent beta-oxa-21:3n-3 molecule, rather than its derivatives (methyl ester, saturated, monohydroperoxy, or monohydroxy forms), is exclusively responsible for attenuation of LTB(4) formation. beta-Oxa-21:3n-3 inhibits the conversion of [(3)H]20:4n-6 to [(3)H]5-hydroxyeicosatetraenoic acid and [(3)H]LTB(4) by neutrophils in the presence of calcium ionophore and also suppresses the activity of purified 5-lipoxygenase, but not cyclooxygenase 1 and 2. Beta-oxa-21:3n-3 is taken up by neutrophils and incorporated into phospholipids and neutral lipids. In the presence of calcium ionophore, the leukocytes convert a marginal amount of beta-oxa-21:3n-3 to a 16-monohydroxy-beta-oxa-21:3n-3 derivative. After administration to rodents by gavage or i.p. injection, beta-oxa-21:3n-3 is found to be incorporated into the lipids of various tissues. Thus, beta-oxa-21:3n-3 has the potential to be used in the treatment of inflammatory diseases, which are mediated by products of the lipoxygenase pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/5-hydroxy-6,8,11,14-eicosatetraenoic..., http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents..., http://linkedlifedata.com/resource/pubmed/chemical/Arachidonate 5-Lipoxygenase, http://linkedlifedata.com/resource/pubmed/chemical/Calcimycin, http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol Esters, http://linkedlifedata.com/resource/pubmed/chemical/Diglycerides, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Unsaturated, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyeicosatetraenoic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Leukotriene B4, http://linkedlifedata.com/resource/pubmed/chemical/Lipoxygenase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipids, http://linkedlifedata.com/resource/pubmed/chemical/beta-Oxa 21-3n-3 fatty acid
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
171
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4773-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Inhibition of neutrophil leukotriene B4 production by a novel synthetic N-3 polyunsaturated fatty acid analogue, beta-oxa 21:3n-3.
pubmed:affiliation
Department of Immunopathology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't