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Protective effects of Y-27632 on hypoxia/reoxygenation-induced intestinal injury in newborn rats.

AbstractBACKGROUND/PURPOSE:
Necrotizing enterocolitis (NEC) is a major cause of mortality in neonates and is associated with a disruption in the protective intestinal barrier. The precise cause of NEC is elusive. However, ischemia/reperfusion injury of the intestine has been considered a major contributing factor. We examined the role of Y-27632, a selective Rho-kinase inhibitor, on a hypoxia/reoxygenation (H/R)-induced intestinal injury of newborn rat pups.
METHODS:
Hypoxia/reoxygenation was achieved by placing rat pups in an airtight chamber aerated with 95% N(2) + 5% CO(2) for 10 minutes followed by 10-minute 100% oxygen. Forty newborn rat pups were randomly allocated into 4 groups. Group 1 served as untreated controls. The pups in group 2 were subjected to H/R only. In groups 3 and 4, the rats were treated with intraperitoneal injection of 0.3 and 3 mg kg(-1) day(-1) of Y-27632 for 5 days following H/R, respectively. The pups were killed 6 days following the H/R injury. Intestine specimens were evaluated for histopathology and biochemical investigation.
RESULTS:
The microscopic lesions in H/R rat pups were virtually the same as those seen in neonatal NEC, with severe destruction of villi and crypts. Hypoxia/reoxygenation resulted in significant elevation in malondialdehyde levels, but decreased tissue nitric oxide levels (P < .05). Protective effects of Y-27632 on H/R-induced intestinal injury of newborn rat pups were observed with a significant decrease in the intestinal injury score, suppression in malondialdehyde levels, and increase in nitric oxide levels (P < .05).
CONCLUSIONS:
In this experimental study, Y-27632 significantly attenuated H/R-induced intestinal injury. These findings indicate that inhibition of Rho-kinase may offer a novel therapeutic approach in the treatment of NEC.
AuthorsGül Balyemez, Ercan Sivasli, Haluk Ceylan, Ediz Tutar, Sule Ekiz, Mehmet Tarakcioglu, Abdullah T Demiryurek, M Yavuz Coskun
JournalJournal of pediatric surgery (J Pediatr Surg) Vol. 46 Issue 8 Pg. 1490-4 (Aug 2011) ISSN: 1531-5037 [Electronic] United States
PMID21843713 (Publication Type: Journal Article)
CopyrightCopyright © 2011 Elsevier Inc. All rights reserved.
Chemical References
  • Amides
  • Enzyme Inhibitors
  • Pyridines
  • Y 27632
  • Carbon Dioxide
  • Nitric Oxide
  • Malondialdehyde
  • Nitrogen
  • Oxygen
Topics
  • Amides (administration & dosage, pharmacology, therapeutic use)
  • Animals
  • Anoxia (complications)
  • Carbon Dioxide (administration & dosage)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Enterocolitis, Necrotizing (drug therapy, etiology, metabolism)
  • Enzyme Inhibitors (administration & dosage, pharmacology, therapeutic use)
  • Intestinal Mucosa (drug effects, metabolism, pathology)
  • Intestines (drug effects, metabolism, pathology)
  • Malondialdehyde (metabolism)
  • Nitric Oxide (metabolism)
  • Nitrogen (administration & dosage)
  • Oxygen (administration & dosage)
  • Pyridines (administration & dosage, pharmacology, therapeutic use)
  • Random Allocation
  • Rats
  • Rats, Wistar

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