Paraquat-induced formation of leukotriene B sub(4) in rat lungs: Modulation by N-acetylcysteine

The present work is focused on the formation of the inflammatory mediator leukotriene B sub(4) (LTB sub(4)) in the lungs of paraquat (PQ)-intoxicated rats. The levels of LTB sub(4) and the number of neutrophils in lung lavages 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 (NAC), 8 h after PQ, inhibited this effect. The release of LTB sub(4) from alveolar macrophages (AM) or alveolar epithelial type II cells from healthy animals incubated with PQ and/or NAC did not offer an explanation for the effect of these chemicals on LTB sub(4) in the bronchoalveolar lavage fluid (BALF). The PQ-enhanced, NAC-inhibited release of arachidonic acid (AA) by alveolar epithelial type II cells did, however, explain our in vivo results, when one assumes that the AM synthesize their 5-lipoxygenase products from alveolar epithelial cell-derived AA, an hypothesis demonstrated already by other researchers.