Revisiting ischemia and reperfusion injury as a possible cause of necrotizing enterocolitis: Role of nitric oxide and superoxide dismutase.

Abstract

BACKGROUND/PURPOSE:

The pathogenesis of necrotizing enterocolitis (NEC) is unknown. Ischemia and reperfusion (I/R) injury has been considered a major contributing factor. Nitric oxide (NO) and superoxide dismutases (SODs) have been shown to protect bowel from I/R injury. This study aims to assess (1) the ability of premature intestine to resist I/R injury compared with mature intestine and (2) the possible role of NO and SODs in modulating such response.

METHODS:

Intestines from 5 groups of rats (n = 6 for each study group) were studied: (1) premature, gestational age 20 days; (2) premature, gestational age 22 days; (3) full-term, newborn; (4) infant, day 15; (5) infant, day 30.

EXPERIMENTS:

(1) The degrees of I/R injury after 0, 30, 60, 90 and 120 minutes, respectively, of ischemia and 25 minutes of I/R were assessed histologically by a pathologist who was unaware of the operative details. (2) Tissue NO and copper levels were measured by electroparamagnetic resonance (EPR) study; and nitric oxide synthases, copper zinc (CuZn) SODs and manganese (Mn) SODs were examined immunohistochemically. (3) and (4) I/R injury was assessed in rats that had received intraperitoneal injections of L-arginine (NO donor) and L-NAME (NO antagonist), respectively.

RESULTS:

For premature (1,2), newborn (3) and mature (4,5) intestines, grades of injury at maximum I/R period studied (120 minutes of ischemia, 25 minutes of reperfusion) were 0, 0, and 3, respectively (P <.05); NO levels were 1 u +/- 1.5, 3 +/- 2.5, and 22 u +/- 3.5, respectively (P <.05); Cu levels were 150 u +/- 15, 200 u +/- 41 and 12 u +/- 2, respectively (P <.05); NOS in intestines were +, +, +++ and CuZnSODs were ++, +++, +, respectively; and MnSODs were +++, ++, -, respectively. No change in NO levels was detected in groups (1), (2), or (3) after L-arginine and L-NAME injections.

CONCLUSIONS:

Premature rat intestine is highly resistant to I/R injury, which may indicate that I/R alone, in the absence of other predisposing factors (eg, bacterial colonization) may not be sufficient in causing NEC. Nitric oxide does not have a protective role for immature and newborn intestines in I/R as in mature intestine. The high level of SODs of the immature and newborn intestine may play an important role in its high resistance to I/R injury.

• Authors: K L Chan, Connie W C Hui, K W Chan, Peter C W Fung, Jana Y H Wo, G Tipoe, Paul K H Tam
• Journal: Journal of pediatric surgery (J Pediatr Surg) Vol. 37 Issue 6 Pg. 828-34 (Jun 2002) ISSN: 1531-5037 [Electronic] United States
• PMID: 12037744 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002, Elsevier Science (USA). All rights reserved.

Chemical References

• Nitric Oxide
• Arginine
• Superoxide Dismutase
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Arginine (administration & dosage)
• Biopsy
• Enterocolitis, Necrotizing (etiology)
• Immunohistochemistry
• Intestine, Small (blood supply, metabolism)
• Ischemia (complications, metabolism)
• NG-Nitroarginine Methyl Ester (administration & dosage)
• Nitric Oxide (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (complications, metabolism)
• Superoxide Dismutase (metabolism)