Document Detail


Contribution of oxygen-derived free radicals to experimental necrotizing enterocolitis.
MedLine Citation:
PMID:  3348358     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oxygen-derived free radicals, particularly superoxide anion, are considered important mediators of intestinal injury induced by ischemia/reperfusion based on the protective effects of superoxide dismutase and allopurinol. A role for free radicals was investigated in a model of necrotizing enterocolitis (NEC) which was initiated by a luminal, as opposed to a vascular, insult. Intestinal loops of weanling rabbits received either saline (control loops) or a solution of 10 mg/ml casein and 50 mg/ml calcium gluconate acidified to pH 4 with proprionic acid (treated loops). When the animals were sacrificed 3 hours later, severe damage was noted in the treated loops, which included blunting of villi and edema, with all animals surviving. At 16 hours only 5 of 8 rabbits survived, and 3 had hemorrhagic necrosis. Control loops were normal in each case. Intravenous infusion of superoxide dismutase (4 mg/kg/hr), commencing 15 minutes after NEC induction, totally prevented intestinal injury. On the other hand, pretreatment with allopurinol, an inhibitor of xanthine oxidase, for 2 days (30 and 60 mg/kg by mouth) was not protective against intestinal damage. A cellular infiltration in treated loops was not histologically evident in the majority of animals at 3 hours after treatment, a finding confirmed by the minimal accumulation of 111In-labeled leukocytes in damaged and intact intestinal tissue. These results suggest that superoxide generated locally from sources other than xanthine oxidase play a critical and early role in experimental NEC and that superoxide dismutase may prove to be an effective therapy in this devastating neonatal disease.
Authors:
D A Clark; D M Fornabaio; H McNeill; K M Mullane; S J Caravella; M J Miller
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of pathology     Volume:  130     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  1988 Mar 
Date Detail:
Created Date:  1988-04-20     Completed Date:  1988-04-20     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  537-42     Citation Subset:  AIM; IM    
Affiliation:
Department of Pharmacology, New York Medical College, Valhalla 10595.
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MeSH Terms
Descriptor/Qualifier:
Allopurinol / pharmacology
Animals
Animals, Newborn
Calcium Gluconate
Enterocolitis, Pseudomembranous / pathology*
Free Radicals
Indium
Intestines / pathology
Oxygen*
Rabbits
Superoxide Dismutase / metabolism
Xanthine Oxidase / antagonists & inhibitors
Chemical
Reg. No./Substance:
0/Free Radicals; 299-28-5/Calcium Gluconate; 315-30-0/Allopurinol; 7440-74-6/Indium; 7782-44-7/Oxygen; EC 1.15.1.1/Superoxide Dismutase; EC 1.17.3.2/Xanthine Oxidase
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