N-Acetylcysteine Attenuates Phorbol Myristate Acetate Induced Lung Injury in Rat Lungs

Introduction: N-Acetylcysteine (NAC) has long served been clinically as a mucolytic agent for chronic bronchitis. It is also a cytoprotective agent through inhibition of the production of pro-inflammatory cytokines and free radicals. Therefore, its role of minimizing inflammatory lung condition, such as acute lung injury (ALI) need to be investigated. Experimental lung injury 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. This study aimed to evaluate the effects of N-Acetylcysteine (NAC) on the PMA-induced ALI and associated changes in rat lung model.Methods: The isolated rat's lung was utilized to investigate the effects of pretreatment of NAC on the ALI and associated changes following administration of PMA. The degree of lung injury was assessed by various parameters including protein concentration, lactate dehydrogenase (LDH) activity, exhaled nitric oxide (NO), total cells and polymorphonuclear leukocyte (PMN) cell counts in the bronchoalveolar lavage fluid (BALF), the pulmonary arterial pressure (PAP) and microvascular permeability (K(subscript fc)), and the concentration of nitrate/nitrite, methyl guanidine (MG), tumor necrosis factor(subscript α) (TNF(subscript α)) and interleukin-1(subscript β) (IL-1(subscript β)) in lung perfusate. In addition, we also evaluate the lung injury by histopathological examination and by grading system for the lung injury score (LIS).Result: PMA caused severe ALI as evidenced by the marked increases in exhaled NO, BALF, histopathological changes, and LIS. It also increased the nitrate/nitrite, MG, TNF(subscript α), and IL-1(subscript β) in lung perfusate (P＜0.05 compared with vehicle group). Pretreatment with NAC significantly attenuated these changes and abrogated the extent of ALI (P＜0.05 compared with the PMA group). Conclusions: Our results suggest that NAC exerts strong protective effects on the PMA-induced ALI and associated alterations. The mechanisms are possibly attributable to it's antioxidant actions, inhibition of pro-inflammatory cytokines, and restoration of glutathione enzymes.

並列關鍵字

N-Acetylcysteine ； phorbol myristate acetate ； acute lung injury

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