PARTICIPATION OF NITRIC OXIDE AND PEROXYNITRITE ANION IN EMBRYONIC RESORPTION DUE TO LPS

AISEMBERG J; OGANDO D; RIBEIRO, M L; FRANCHI AM

ADVANCES IN CHEMISTRY AND BIOLOGY OF NITRIC OXIDE

Research Signpost

Lugar: Kerala, India; Año: 2007; p. 227 - 240

Nitric oxide (NO) fulfills important functions during pregnancy: implantation, decidualization, vasodilatation and myometrial relaxation. However, in high concentrations such as the ones that are produced in sepsis, it has toxic effects since it is a free radical. Maternal infections are a cause of abort and preterm labor in humans but their mechanism are not clear. Spontaneous and cytokine-boosted abortion rates have been linked to exposure to environmental LPS. We have developed a murine model to study the mechanism of septic abortion by inducing embryonic resorption with LPS. In early pregnancy, low doses of LPS that reproduce most of the systemic and cellular effects of sepsis, without affecting maternal survival, produce high percentage of embryonic resorption. In the implantation sites the induction of abortion by LPS increases NO synthesis. Aminoguanidine (AG), an inhibitor of inducible NOsynthase activity, partially reversed LPS-induced embryonic resorption. Indirect effects will occur under a high and sustained flux of NO and will result in toxic consequences, which include oxidation, nitrosation and nitration reactions. In our model, LPS increased the oxidative damage, evidenced by tyrosine proteins nitration, due to the production of peroxynitrite anions. These results show that NO fulfills a fundamental role in LPS induced embryonic resorption.