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Titolo:
Polynitroxyl-albumin (PNA) plus tempol attenuate lung capillary leak elicited by prolonged intestinal ischemia and reperfusion
Autore:
Zhang, S; Li, HQ; Ma, L; Trimble, CE; Kuppusamy, P; Hsia, CJC; Carden, DL;
Indirizzi:
SynZyme Technol LLC, Irvine, CA 92630 USA SynZyme Technol LLC Irvine CA USA 92630 Technol LLC, Irvine, CA 92630 USA Johns Hopkins Med Inst, Div Cardiol, Baltimore, MD 21205 USA Johns HopkinsMed Inst Baltimore MD USA 21205 ol, Baltimore, MD 21205 USA Johns Hopkins Med Inst, EPR Ctr, Baltimore, MD 21205 USA Johns Hopkins MedInst Baltimore MD USA 21205 tr, Baltimore, MD 21205 USA Louisiana State Univ, Med Ctr, Dept Internal Med, Shreveport, LA USA Louisiana State Univ Shreveport LA USA Internal Med, Shreveport, LA USA Louisiana State Univ, Med Ctr, Dept Physiol & Biophys, Shreveport, LA USA Louisiana State Univ Shreveport LA USA iol & Biophys, Shreveport, LA USA
Titolo Testata:
FREE RADICAL BIOLOGY AND MEDICINE
fascicolo: 1, volume: 29, anno: 2000,
pagine: 42 - 50
SICI:
0891-5849(20000701)29:1<42:P(PTAL>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
RESPIRATORY-DISTRESS SYNDROME; NEUTROPHIL APOPTOSIS; OXIDATIVE STRESS; FREE-RADICALS; INJURY; NITROXIDE; RAT; INTERLEUKIN-1; ARDS; ANTIOXIDANTS;
Keywords:
ARDS; capillary permeability; nitroxide; polynitroxyl albumin; intestinal ischemia/reperfusion; free radicals;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Hsia, CJC SynZyme Technol LLC, 1 Technol Dr,Suite E-309, Irvine, CA 92630 USA SynZyme Technol LLC 1 Technol Dr,Suite E-309 Irvine CA USA 92630
Citazione:
S. Zhang et al., "Polynitroxyl-albumin (PNA) plus tempol attenuate lung capillary leak elicited by prolonged intestinal ischemia and reperfusion", FREE RAD B, 29(1), 2000, pp. 42-50

Abstract

Stable nitroxyl radicals (nitroxides) are potential antioxidant drugs, andwe have previously reported that linking nitroxide to biological macromolecules can improve therapeutic activity in at least two ways. First, polynitroxylated compounds such as polynitroxyl human serum albumin (PNA) are a novel class of high molecular weight, extracellular antioxidants. Second, compounds such as PNA can prolong the half-life of free (unbound, low molecular weight) nitroxides such as 3-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl(Tempol) in vivo. Unlike PNA, Tempol can readily access the intracellular compartment. Thus PNA can act alone in the extracellular compartment, or inconcert with Tempol, to provide additional antioxidant protection within cells. In this study, we compared the abilities of PNA, Tempol, and the combination of PNA + Tempol to prevent lung microvascular injury secondary to prolonged gut ischemia (I, 120 min) and reperfusion (R, 20 min) in the rat. Pulmonary capillary filtration coefficient (K-f.c) and lung neutrophil retention (tissue myeloperoxidase activity, MPO) were measured in normal, isolated rat lungs pet-fused with blood harvested from VR rats. Blood donor ratswere treated with drug during ischemia. Gut YR resulted in a marked increase in pulmonary capillary coefficient and lung MPO. PNA + Tempol, but not PNA alone or Tempol alone, at the doses used, prevented the development of lung leak. None of the treatments had an effect on lung neutrophil retention. Anti-inflammatory therapeutic activity appeared to correlate with blood Tempol level: in the presence of PNA, blood Tempol levels were maintained inthe 50-100 mu M range vs. essentially undetectable levels shortly after Tempol was administered alone. In this model of lung injury secondary to prolonged gut I/R, lung capillary leak was prevented when the membrane-permeable compound Tempol was maintained in its active, free radical state by PNA. (C) 2000 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 01:36:35