Document Detail

Oxidative stress during post-hypoxic-ischemic reperfusion in the newborn lamb: the effect of nitric oxide synthesis inhibition.
MedLine Citation:
PMID:  9078529     Owner:  NLM     Status:  MEDLINE    
Post-hypoxic-ischemic (HI) reperfusion induces endothelium and neurons to produce excessive amounts of nitric oxide and superoxide, leading to peroxynitrite formation, release of protein-bound metal ions (i.e. iron), and cytotoxic oxidants. We produced severe HI in 18 newborn lambs and serially determined plasma prooxidants (non-protein-bound iron), lipid peroxidation (malondialdehyde), and antioxidative capacity [ratio of ascorbic acid/dehydroascorbic acid (AA/DHA), alpha-tocopherol, sulfhydryl groups, allantoin/uric acid ratio, and vitamin A] in blood effluent from the brain before and at 15, 60, 120, and 180 min after HI. The lambs were divided in three groups: six received a placebo (CONT), six received low dose (10 mg/kg/i.v.) N omega-nitro-L-arginine (NLA-10) to block nitric oxide production, and six received high dose NLA (40 mg/kg/i.v.; NLA-40), immediately after completion of HI. Non-protein-bound iron increased in all groups after HI but was significantly lower in both NLA groups at 180 min post-HI (p < 0.05), the AA/DHA ratio showed a consistent decrease in CONT (at 60 min post-HI, p < 0.05), but remained stable in NLA lambs. alpha-Tocopherol decreased steadily in the CONT, but not in the NLA lambs [180 post-H: 1.9 +/- 0.9 versus 4.2 +/- 0.7 microM (NLA-40), p < 0.05). Malondialdehyde was significantly higher in CONT lambs 120 min post-H compared with NLA groups [0.61 +/- 017 versus 0.44 +/- 0.05 microM (NLA-40), p < 0.05]. Vitamin A and sulfhydryl groups did not differ among groups. We conclude that post-H inhibition of nitric oxide synthesis diminishes non-protein-bound iron increment and preserves antioxidant capacity.
C A Dorrepaal; F van Bel; R M Moison; M Shadid; M van de Bor; P Steendijk; H M Berger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pediatric research     Volume:  41     ISSN:  0031-3998     ISO Abbreviation:  Pediatr. Res.     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-07-01     Completed Date:  1997-07-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  321-6     Citation Subset:  IM    
Department of Pediatrics (Division of Neonatology), Leiden University Hospital, The Netherlands.
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MeSH Terms
Animals, Newborn
Antioxidants / metabolism
Brain Ischemia / drug therapy*
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Enzyme Inhibitors / therapeutic use*
Hypoxia, Brain / drug therapy*
Lipid Peroxidation / drug effects
Nitric Oxide Synthase / antagonists & inhibitors*
Nitroarginine / therapeutic use*
Oxidative Stress / drug effects
Reperfusion Injury / drug therapy*
Reg. No./Substance:
0/Antioxidants; 0/Enzyme Inhibitors; 2149-70-4/Nitroarginine; EC Oxide Synthase

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

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