Document Detail


Differential expression pattern of heme oxygenase-1/heat shock protein 32 and nitric oxide synthase-II and their impact on liver injury in a rat model of hemorrhage and resuscitation.
MedLine Citation:
PMID:  10628624     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To investigate the role of the vasodilator systems heme oxygenase-1/heat shock protein 32 (HO-1/HSP32) and nitric oxide synthase-II (NOS-II), generating carbon monoxide and nitric oxide respectively, as modulators of liver injury in an experimental model of reversible hemorrhagic shock. DESIGN: Prospective controlled laboratory study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats weighing 250-350 g. INTERVENTIONS: Animals were anesthetized and assigned to a hemorrhagic shock (mean arterial pressure, 35-40 mmHg for 60 mins) or a sham protocol. On the basis of the time course of gene expression, HO-1/HSP32 or NOS-II was blocked 5 hrs after onset of resuscitation. To assess the role of the antioxidative properties of the heme oxygenase (HO) pathway in additional experiments, Trolox, a potent antioxidant, was administered at the time of blockade of HO. Liver injury was assessed morphometrically and by plasma alpha-glutathione-S-transferase (alpha-GST) release 11 hours after onset of resuscitation. MEASUREMENTS AND MAIN RESULTS: Hemorrhage and resuscitation increased HO-1/HSP32 messenger RNA and protein primarily in parenchymal cells, and a faint induction of NOS-II, restricted to nonparenchymal cells, was observed. Inhibition of the HO pathway with tin protoporphyrin-IX (SnPP-IX) increased the incidence of pericentral necrosis (intact acini: shock/vehicle 68.8%; shock/SnPP-IX 42.6%) and alpha-GST levels (sham 94+/-24 microg/L; shock/vehicle 377+/-139 microg/L; shock/SnPP-IX 1708+/-833 microg/L), whereas blockade of NOS-II with S-methylisothiourea did not affect liver injury. Coadministration of Trolox failed to attenuate the aggravation of necrosis associated with blockade of HO, whereas alpha-GST levels were reduced (intact acini: shock/vehicle/Trolox 82.1%, shock/SnPP-IX/Trolox 42.7%; alpha-GST: shock/vehicle/Trolox 202+/-55 microg/L; shock/SnPP-IX/Trolox 236+/-61 microg/L). CONCLUSIONS: These data suggest that HO-1/HSP32, but not the alternative cyclic guanosine monophosphate-generating enzyme NOS-II, is induced after hemorrhage and resuscitation and protects against hepatocellular injury. Both metabolites generated by the heme oxygenase pathway, e.g., carbon monoxide (a vasodilator) and biliverdin (an antioxidant) seem to contribute to the salutary effects of induction of HO-1/HSP32.
Authors:
H Rensing; I Bauer; V Datene; C Pätau; B H Pannen; M Bauer
Related Documents :
17712624 - Neuroprotective effects of cactus polysaccharide on oxygen and glucose deprivation indu...
17523944 - Increased asymmetric dimethylarginine concentrations in stimulated peripheral blood mon...
8667214 - Nitric oxide mediates the inhibitory action of platelet-activating factor on angiotensi...
7555034 - Potent activation of nitric oxide synthase by garlic: a basis for its therapeutic appli...
7513534 - Aprotinin effect on platelet function and clotting during cardiopulmonary bypass.
23700004 - Bone tissue engineering with bone marrow-derived stromal cells integrated with concentr...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  27     ISSN:  0090-3493     ISO Abbreviation:  Crit. Care Med.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-01-27     Completed Date:  2000-01-27     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2766-75     Citation Subset:  AIM; IM    
Affiliation:
Department of Anesthesiology and Critical Care Medicine, University of the Saarland, Homburg, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Carbon Monoxide / metabolism
Gene Expression Regulation, Enzymologic
Glutathione Transferase / blood
Heat-Shock Proteins / metabolism*
Heme Oxygenase (Decyclizing) / genetics,  metabolism*
Hemodynamics / drug effects
Liver / enzymology*,  pathology
Male
Nitric Oxide / biosynthesis
Nitric Oxide Synthase / genetics,  metabolism*
Rats
Rats, Sprague-Dawley
Resuscitation
Shock, Hemorrhagic / metabolism*,  therapy
Chemical
Reg. No./Substance:
0/Heat-Shock Proteins; 10102-43-9/Nitric Oxide; 630-08-0/Carbon Monoxide; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.99.3/Heme Oxygenase (Decyclizing); EC 2.5.1.18/Glutathione Transferase
Comments/Corrections
Comment In:
Crit Care Med. 1999 Dec;27(12):2842-3   [PMID:  10628645 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Gut mucosal-arterial Pco2 gradient as an indicator of splanchnic perfusion during systemic hypo- and...
Next Document:  Effect of endotracheal suctioning on cerebral oxygenation in traumatic brain-injured patients.