Effect of N-Acetylcysteine on the Superoxide Release, Chemotaxis from the Neutrophils and Glutathione Level of Plasma and Neutrophils

Song, Jeong Sup; Lee, Sook Young; Moon, Hwa Sik; Park, Sung Hak

Abstract

BACKGROUND
N-acetylcysteine(ACE) is used both orally and intravenously in a variety of experimental pathologies resembling human disease states which exhibit endothelial toxicity as a result of oxidative stress, including acute pulmonary oxygen toxicity, septicemia and endotoxin shock. Despite these observations in vivo, it is not certain how this thiol drug produces its protective effects. ACE is a cysteine derivative which is able to directly react with oxygen radicals and may also act as a cysteine and glutathione(GSH) precursor following deacetylation. In this paper, we tried to know whether the therapeutic doses of ACE can modify the inflammatory function of the neutrophils and can increase the glutathione level of plasma in chronic obstructive pulmonary disease(COPD) patients. In addition, the effect of ACE to the purified neutrophil in terms of superoxide release and glutathione synthesis were observed. METHOD: Firstly, we gave 600mg of ACE for seven days and compare the release of superoxide, luminol-enhanced chemiluminescence from the neutrophils, neutrophil chemotaxis, and plasma GSH levels before and after ACE treatment in COPD patients. Secondly, we observed the dose dependent effect of ACE to the purified neutrophil's superoxide release and GSH levels in vitro.
RESULTS
1) Usual oral therapeutic doses(600mg per day) of ACE for seven days did affect neither on the neutrophils superoxide release, chemiluminescence, chemotaxis, nor on the plasma GSH concentration in the COPD patients. 2) ACE decreases the purified neutrophil's superoxide release and increase the GSH production in dose dependent fashion in vitro.
CONCLUSION
Despite the fact that oral ACE treatment did not affect on the neutrophil's inflammatory function and plasma GSH concentration in COPD patients in usual therapeutic doses, it decreases the superoxide release and increases the GSH production from the isolated neutrophils in high molar concentrations. These findings suggest that to obtain an antioxidative effects of ACE, it might be needed to increase the daily dosage of ACE or therapeutic duration or change the route of adminisration in COPD patients.