Paraquat-induced formation of leukotriene B4 in rat lungs: modulation by N-acetylcysteine.
The present work is focused on the formation of the inflammatory mediator leukotriene B4 (LTB4) in the lungs of paraquat (PQ)-intoxicated rats. The levels of LTB4 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 LTB4 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 LTB4 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.
Hoffer
E
E
Israel Poison Information Center, Rambam Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Shenker
L
L
Baum
Y
Y
Tabak
A
A
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000473:pathology; D010269:Paraquat / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D007975:Leukotriene B4; D016718:Arachidonic Acid; D010269:Paraquat; D000111:Acetylcysteine