N-acetylcysteine attenuates the acute lung injury caused by phorbol myristate acetate in isolated rat lungs

I. Chun Chuang, Demeral David Liu, Shang Jyh Kao, Hsing I. Chen

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Acute lung injury (ALI) caused by phorbol myristate acetate (PMA) is characterized by pulmonary edema and inflammatory cells infiltration. PMA-activated neutrophils in vivo and in vitro to release free radicals, pro-inflammatory cytokines, nitric oxide (NO) and other mediators. These mediators may be the causes of pulmonary hypertension and increased microvascular permeability. In the present study, we used isolated perfused rat lungs from Sprague-Dawley (SD) rats. The purpose was to evaluate the effects of pretreatment of N-acetylcysteine (NAC) on the PMA-induced ALI and associated changes. PMA (2 μg kg-1) was introduced into the lung perfusate. NAC (150 mg kg-1) was administered 10 min before PMA. Thirty isolated lungs were randomly assigned to receive vehicle (dimethyl sulfoxide, DMSO, the solvent for PMA, 100 μg g-1), PMA alone and PMA with NAC pretreatment. There were 10 lungs in each group. We measured the lung weight (LW) to body weight (BW) ratio (LW/BW), LW gain (LWG), exhaled nitric oxide (NO) and protein concentration in bronchoalveolar lavage (PCBAL). The pulmonary arterial pressure (PAP) and microvascular permeability (Kfc) were assessed. The concentration of nitrate/nitrite, methyl guanidine (MG), tumor necrosis factorα (TNFα) and interleukin-1β (IL-1β) in lung perfusate were determined. In addition, we also evaluate the lung injury by histopathological examination and by grading system for the lung injury score (LIS). PMA caused severe ALI as evidenced by the marked increases in LW changes, exhaled NO, PCBAL, histopathological changes, and LIS. It also increased the nitrate/nitrite, MG, TNFα, and IL-1β in lung perfusate. Pretreatment with NAC significantly attenuated these changes and abrogated the extent of ALI. Our results suggest that NAC exerts strong protective effects on the PMA-induced ALI and associated alterations. The mechanisms are possibly attributable to its antioxidant actions, inhibition of pro-inflammatory cytokines, and restoration of glutathione enzymes.

Original languageEnglish
Pages (from-to)726-733
Number of pages8
JournalPulmonary Pharmacology and Therapeutics
Volume20
Issue number6
DOIs
Publication statusPublished - Dec 2007

Keywords

  • Acute lung injury
  • Free radical
  • N-acetylcysteine
  • Phorbol myristate acetate
  • Pro-inflammatory cytokines

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmacology

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