ABSTRACT
BACKGROUND/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.
Subject(s)
Amides/pharmacology , Enterocolitis, Necrotizing/drug therapy , Enzyme Inhibitors/pharmacology , Hypoxia/complications , Intestinal Mucosa/drug effects , Intestines/drug effects , Pyridines/pharmacology , Amides/administration & dosage , Amides/therapeutic use , Animals , Carbon Dioxide/administration & dosage , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Administration Schedule , Enterocolitis, Necrotizing/etiology , Enterocolitis, Necrotizing/metabolism , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/therapeutic use , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Intestines/pathology , Malondialdehyde/metabolism , Nitric Oxide/metabolism , Nitrogen/administration & dosage , Oxygen/administration & dosage , Pyridines/administration & dosage , Pyridines/therapeutic use , Random Allocation , Rats , Rats, WistarABSTRACT
Diffuse alveolar haemorrhage (DAH) is indicated by the presence of red blood cells, fibrin and haemosiderin deposits in the lung parenchyma. We present a case of DAH in a 25-year-old male following 5-nitroimidazole treatment. The first episode of haemoptysis occurred following metronidazole treatment 10 months previously. The second episode of haemoptysis occurred following ornidazole treatment 10 days before admission. During his first admission, the patients haemoglobin concentration decreased to 40 g/L. The CXR was normal, whereas high resolution CT of the lungs revealed a diffuse acinonodular pattern. Serological tests for connective tissue diseases were negative. The haemorrhagic appearance of the BAL fluid obtained during fibreoptic bronchoscopy was consistent with DAH. Microbiological analysis of the BAL fluid showed no evidence for bacterial or mycobacterial infection. Haemosiderin laden macrophages were detected in BAL fluid and lung biopsy specimens. DAH due to use of 5-nitroimidazole was diagnosed on the basis of the patient's previous history and complete recovery following treatment with corticosteroid. This is the first reported case of DAH due to use of 5-nitroimidazole. Physicians should be aware of this side-effect when prescribing this group of drugs to patients.
