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.

The effect of N-acetyl cysteine on serum glutathione, TNF-α and tissue malondialdehyde levels in the treatment of sepsis

“…[17] In another experimental sepsis model created by endotoxin administration to rats, it was found that histopathological findings such as alveolar and interstitial hemorrhage and edema and leukocyte infiltration improved in groups treated with high doses of NAC. [18] In our study, in the histopathological examination of the lungs, the increase in PMNL was found to have significantly decreased in the NAC group compared to the sepsis group. The improvements in congestion, hemorrhage and septal thickening in the lung tissue and the histological improvements in the kidney and the liver were not statistically significant.…”

Effect of N-acetylcysteine on pulmonary cell death in a controlled hemorrhagic shock model in rats

“…Other studies also confirm the protective role of NAC in lung cell death in experimental models of sepsis 18,22,23 .…”

“…However, there is evidence that NAC is able to attenuate apoptosis of lung epithelial cells in experimental models of sepsis 18 .…”

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“…A tissue damage evaluation scale was used as was stated in an article by Özdülger et al (12). In this scale:…”