Dexamethasone attenuates neutrophil infiltration in the rat kidney in ischemia/reperfusion injury: the possible role of nitroxyl.
Neutrophil infiltration to the tissue, which is one of the important pathogenetic factors in ischemia/reperfusion injury, can be inhibited by glucocorticoids. The purpose of the present study was to clarify the mechanisms by which glucocorticoids inhibit neutrophil infiltration in renal ischemia/reperfusion injury in rats. Pretreatment with dexamethasone significantly attenuated the enhanced neutrophil infiltration and expression of intercellular adhesion molecule-1 induced by renal ischemia/reperfusion. Treatment with nitroxyl anion releaser known as Angeli's salt abolished the beneficial effect of dexamethasone in renal ischemia/reperfusion. Renal dysfunction and tubular damage induced by renal ischemia/reperfusion were not ameliorated by pretreatment with dexamthasone. These results indicate that the attenuation by dexamethasone of neutrophil infiltration and intercellular adhesion molecule-1 expression during renal ischemia/reperfusion may be mediated by the suppressed production of nitroxyl anion. Thus, neutrophil infiltration in renal ischemia/reperfusion injury may be mediated, at least in part, by the enhanced production of nitroxyl anion.
Takahira
R
R
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Yonemura
K
K
Fujise
Y
Y
Hishida
A
A
D000818:Animals; D000838:Anions; D003907:Dexamethasone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000473:pathology*; D009573:Nitrites / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology*
D000838:Anions; D005938:Glucocorticoids; D009573:Nitrites; D009589:Nitrogen Oxides; D018799:Intercellular Adhesion Molecule-1; C021229:oxyhyponitrite; D003907:Dexamethasone; C039900:nitroxyl