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

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.
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.
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).
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
  • 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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: