PARAQUAT-INDUCED FORMATION OF LEUKOTRIENE B-4 IN RAT LUNGS - MODULATION BY N-ACETYLCYSTEINE

The present work is focused on the formation of the inflammatory media tor leukotriene B-4 (LTB(4)) in the lungs of paraquat (PQ)-intoxicated rats. The levels of LTB(4) and the number of neutrophils in lung lava ges of PQ-intoxicated rats, measured 12 h after 30 mg/kg PQ, increased significantly compared with those of control animals; administration of 50 mg/kg IP N-acetylcysteine (NAG), 8 h after PQ, inhibited this ef fect. The release of LTB(4) from alveolar macrophages (AM) or alveolar epithelial type II cells from healthy animals incubated with PQ and/o r NAG did not offer an explanation for the effect of these chemicals o n LTB(4) in the bronchoalveolar lavage fluid (BALF). The PQ-enhanced, NAG-inhibited release of arachidonic acid (AA) by alveolar epithelial type II cells did, however, explain our in vivo results, when one assu mes that the AM synthesize their 5-lipoxygenase products from alveolar epithelial cell-derived AA, an hypothesis demonstrated already by oth er researchers. Copyright (C) 1996 by Elsevier Science Inc.