title: Consecutive administration of paraquat to rats induces enhanced cholesterol peroxidation and lung injury.
abstract: It is our hypothesis that as a consequence of increased oxidative stress, rats develop lung injury with increased cholesterol-derived hydroperoxides and oxysterols in lung after consecutive exposure of the rats to paraquat. To test this we administered 10 mg/kg of paraquat i.p. once or seven times (once a day) to Wistar rats. Rats were killed, and lung tissue was collected 24 h after the last paraquat injection. We found that in response to consecutive paraquat doses, there were significant increases in 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH and 7beta-OOH; P=0.01) as well as 7alpha- and 7beta-hydroxycholesterol (7alpha-OH and 7beta-OH; P=0.01), and 7-ketocholesterol (7-keto; P=0.03). In addition, pulmonary hemorrhage, thickening of alveolar septum, and inflammatory cell infiltration of macrophages were observed. This is the first report showing enhanced cholesterol peroxidation and lung injury of rats due to consecutive doses of paraquat.
authors.affiliation: Department of Legal Medicine, Kobe University Graduate School of Medicine, 7 Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Japan. adachi@med.kobe-u.ac.jp
authors.forename: Junko
authors.initials: J
authors.lastname: Adachi
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishii
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tomita
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujita
authors.forename: Yudha
authors.initials: Y
authors.lastname: Nurhantari
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nagasaki
authors.forename: Yasuiro
authors.initials: Y
authors.lastname: Ueno
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry; D004334:Drug Administration Schedule; D005260:Female; D007274:Injections, Intraperitoneal; D007653:Ketocholesterols / Q000009:adverse effects / Q000096:biosynthesis / Q000737:chemistry; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D010269:Paraquat / Q000008:administration & dosage* / Q000009:adverse effects*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013261:Sterols / Q000096:biosynthesis
chemical_list: D007653:Ketocholesterols; D013261:Sterols; C002843:cholesterol hydroperoxide; D002784:Cholesterol; D010269:Paraquat