Document Detail


Nitric oxide mediates prostaglandins' deleterious effect on lipopolysaccharide-triggered murine fetal resorption.
MedLine Citation:
PMID:  17460035     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Genital tract bacterial infections could induce abortion and are some of the most common complications of pregnancy; however, the mechanisms remain unclear. We investigated the role of prostaglandins (PGs) in the mechanism of bacterial lipopolysaccharide (LPS)-induced pregnancy loss in a mouse model, and we hypothesized that PGs might play a central role in this action. LPS increased PG production in the uterus and decidua from early pregnant mice and stimulated cyclooxygenase (COX)-II mRNA and protein expression in the decidua but not in the uterus. We also observed that COX inhibitors prevented embryonic resorption (ER). To study the possible interaction between nitric oxide (NO) and PGs, we administered aminoguanidine, an inducible NO synthase inhibitor. NO inhibited basal PGE and PGF(2alpha) production in the decidua but activated their uterine synthesis and COX-II mRNA expression under septic conditions. A NO donor (S-nitroso-N-acetylpenicillamine) produced 100% ER and increased PG levels in the uterus and decidua. LPS-stimulated protein nitration was higher in the uterus than in the decidua. Quercetin, a peroxynitrite scavenger, did not reverse LPS-induced ER. Our results suggest that in a model of septic abortion characterized by increased PG levels, NO might nitrate and thus inhibit COX catalytic activity. ER prevention by COX inhibitors adds a possible clinical application to early pregnancy complications due to infections.
Authors:
J Aisemberg; C Vercelli; S Billi; M L Ribeiro; D Ogando; R Meiss; S M McCann; V Rettori; A M Franchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-25
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  104     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-05-07     Completed Date:  2007-06-20     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7534-9     Citation Subset:  IM    
Affiliation:
Laboratories of Physiopathology of Pregnancy and Labor, Center for Pharmacological and Botanical Studies, National Research Council, University of Buenos Aires (CEFYBO, CONICET-UBA), Buenos Aires C1121ABG, Argentina. jaisemberg@yahoo.com.ar
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MeSH Terms
Descriptor/Qualifier:
Animals
Cyclooxygenase Inhibitors / pharmacology
Female
Fetal Resorption / chemically induced*,  metabolism*
Isoenzymes / genetics,  metabolism
Lipopolysaccharides / pharmacology*
Male
Mice
Mice, Inbred BALB C
Nitric Oxide / metabolism*
Nitric Oxide Synthase / metabolism
Pregnancy
Prostaglandin-Endoperoxide Synthases / genetics,  metabolism
Prostaglandins / metabolism*
RNA, Messenger / genetics
Reactive Oxygen Species / metabolism
Signal Transduction
Tyrosine / metabolism
Chemical
Reg. No./Substance:
0/Cyclooxygenase Inhibitors; 0/Isoenzymes; 0/Lipopolysaccharides; 0/Prostaglandins; 0/RNA, Messenger; 0/Reactive Oxygen Species; 10102-43-9/Nitric Oxide; 55520-40-6/Tyrosine; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases
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