title: Protective effects of Y-27632 on hypoxia/reoxygenation-induced intestinal injury in newborn rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Faculty of Medicine, Department of Pediatrics, University of Gaziantep, Gaziantep, Turkey.
authors.forename: Gül
authors.initials: G
authors.lastname: Balyemez
authors.forename: Ercan
authors.initials: E
authors.lastname: Sivasli
authors.forename: Haluk
authors.initials: H
authors.lastname: Ceylan
authors.forename: Ediz
authors.initials: E
authors.lastname: Tutar
authors.forename: Sule
authors.initials: S
authors.lastname: Ekiz
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tarakcioglu
authors.forename: Abdullah T
authors.initials: AT
authors.lastname: Demiryurek
authors.forename: M Yavuz
authors.initials: MY
authors.lastname: Coskun
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000860:Hypoxia / Q000150:complications*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009584:Nitrogen / Q000008:administration & dosage; D010100:Oxygen / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D011725:Pyridines; C108830:Y 27632; D002245:Carbon Dioxide; D009569:Nitric Oxide; D008315:Malondialdehyde; D009584:Nitrogen; D010100:Oxygen