OVEREXPRESSION OF INDUCIBLE NITRIC OXIDE SYNTHASE AND CYCLOOXYGENASE - 2 IN RAT ZINC-DEFICIENT LUNG: INVOLVEMENT OF A NFêB- DEPENDENT PATHWAY

NIDIA GOMEZ; DAVICINO ROBERTO; BIAGGIO VERONICA S; BIANCO GERMAN A ; ALVAREZ SILVINA M; FISCHER, PATRICIA; MASNATTA LUCAS; RABINOVICH GABRIEL; GIMENEZ MARIA SOFIA

NITRIC OXIDE-BIOLOGY AND CHEMISTRY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2006 vol. 14 p. 30 - 38

1089-8603

Reactive oxygen and nitrogen species have been implicated in the pathogenesis of pulmonary diseases. The goal of this study was to measure the response of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 enzymes (COX-2) in lung with moderate zinc deWciency. Adult male Wistar rats were divided into two groups receiving (1) a zinc-deWcient diet (ZD) or (2) a zinc-adequate control diet. After 2 months of treatment, the zinc-deWcient group showed a signiWcant pulmonary edema. This was associated to a reduction of protein thiols and to a signiWcant increase of metallothionein and glutathione disulWde levels. In addition, a higher serum and lung NO production in ZD group was positively related to the higher activity and expression of iNOS and COX-2 found in lungs. Western blot analysis revealed increased IB degradation, an indicator of NF-B activation in ZD lungs. Anatomopathologic analysis of ZD lungs showed an increase of connective tissue Wbers with an inXux of polymorphonuclear cells. These cells and type II cells from the alveoli showed speciWc immunohistochemical signals for iNOS. The conclusion is that, during the development of zinc-deWciency, iNOS activity increases in lung and contributes to lung injury. Zinc deWciency implications must be taken into account to design therapies and public health interventions involving targeted zinc supplementation for high-risk subjects or certain diseases, such as asthma.  2005 Elsevier Inc. All rights reserved.