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J Pediatr Surg. 2002 Jun;37(6):828-34.

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

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Departments of Surgery, Medicine, Pathology, and Anatomy, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong SAR, China.



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.


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.


(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.


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.


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.

[Indexed for MEDLINE]

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