title: The protective effect of N-acetylcysteine on apoptotic lung injury in cecal ligation and puncture-induced sepsis model.
abstract: Apoptotic loss of parenchymal cells may lead to organ dysfunctions in critically ill patients with septic states. As an antioxidant, the protective effects of N-acetylcysteine (NAC) are documented in many experimental and clinical studies. In this experimental study, we investigated the role of chronically used NAC in septic lung injury on a cecal ligation and puncture (CLP) model. To evaluate this, 30 male Wistar rats were randomly divided into four groups as sham (n = 7), CLP (n = 8), sham + NAC (n = 7) and CLP + NAC (n = 8) groups. NAC was administered 150 mg kg(-1) day through intramuscular route beginning 6 h after the operations and lasting for a period of 1 week. One week later, histopathology and epithelial apoptosis were assessed by hematoxylin-eosin and immunohistochemically by M30 and caspase 3 staining to demonstrate septic lung injury. Additionally, lung tissue myeloperoxidase (MPO) activity, malondialdehyde (MDA), and nitrite/nitrate levels were measured. The MPO activity and MDA levels in lung homogenates were found to be increased in CLP group and the administration of NAC prevented their increase significantly (P < 0.05). However, there were no significant differences among the groups regarding nitrite/nitrate levels. The number of apoptotic cells was significantly lower in CLP+NAC group than CLP group, and this finding was supported by M30 and caspase 3 expression in lung (P < 0.05). Lung histopathology was also protected by NAC in CLP-induced sepsis. In conclusion, the chronic use of NAC inhibited MPO activity and lipid peroxidation, which resulted in reduction of apoptosis in lung in this CLP model. Because lung tissue nitrite/nitrate levels did not change significantly, organs other than the lungs may be responsible for producing the increased nitric oxide during sepsis. The chronic use of NAC needs further investigation for its possible antiapoptotic potential in septic states besides its documented antioxidant and antiinflammatory effects.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Mersin University School of Medicine, Mersin, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Ozdulger
authors.forename: Ismail
authors.initials: I
authors.lastname: Cinel
authors.forename: Oguz
authors.initials: O
authors.lastname: Koksel
authors.forename: Leyla
authors.initials: L
authors.lastname: Cinel
authors.forename: Dincer
authors.initials: D
authors.lastname: Avlan
authors.forename: Ali
authors.initials: A
authors.lastname: Unlu
authors.forename: Hulya
authors.initials: H
authors.lastname: Okcu
authors.forename: Murat
authors.initials: M
authors.lastname: Dikmengil
authors.forename: Ugur
authors.initials: U
authors.lastname: Oral
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002432:Cecum / Q000293:injuries; D004195:Disease Models, Animal; D007416:Intestinal Perforation / Q000150:complications*; D008026:Ligation; D015227:Lipid Peroxidation; D008168:Lung / Q000737:chemistry; D008171:Lung Diseases / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009566:Nitrates / Q000032:analysis; D009573:Nitrites / Q000032:analysis; D018384:Oxidative Stress; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications*
chemical_list: D009566:Nitrates; D009573:Nitrites; D008315:Malondialdehyde; D009195:Peroxidase; D000111:Acetylcysteine