title: Effect of melengestrol acetate on development of 3-methylindole-induced pulmonary edema and emphysema in sheep.
abstract: The involvement of melengestrol acetate (MGA) in susceptibility to developing pulmonary edema and emphysema following oral administration of 3-methylindole (3MI) was investigated using 10 Suffolk ewes receiving 0 or 0.15 mg of MGA daily (n = 5). Blood, urine and ruminal fluid were collected immediately prior to 3MI dosing (0.2 g/kg BW) and 1, 2, 3, 4, 5, 6, 12 and 24 h (blood); 3, 6, 9, 12 and 15 h (urine) and 1, 2, 3 and 12 h (ruminal fluid) afterward. Ewes receiving MGA experienced earlier (P < 0.05) onset of respiratory distress than the control ewes (2.5 vs 4 h), and upon euthanasia at 96 h, their lung weight relative to body weight tended (P < 0.10) to be lower. Ruminal 3MI concentrations did not differ between treatments (P > 0.05). Ewes receiving MGA had higher (P < 0.05) concentrations of 3MI metabolites in plasma prior to dosing than did control ewes, and these values tended to remain higher throughout the sampling period. Immunoreactivity assays indicated more pneumotoxin present in the lungs of MGA-treated ewes than controls. Lung damage was apparently more acute and accelerated in the MGA-treated ewes than in the controls. Urinary 3MI mercapturate concentrations differed (control > MGA-treated, P < 0.05) at 9, 12, and 15 h, but this difference was not apparent when urinary production (as estimated by creatinine concentration) was considered. The implications of these findings for MGA-treated feedlot heifers are currently under investigation.
authors.affiliation: Alberta Agriculture, Food and Rural Development, Medicine Hat, Alberta.
authors.forename: J D
authors.initials: JD
authors.lastname: Popp
authors.forename: T A
authors.initials: TA
authors.lastname: McAllister
authors.forename: J P
authors.initials: JP
authors.lastname: Kastelic
authors.forename: W
authors.initials: W
authors.lastname: Majak
authors.forename: M
authors.initials: M
authors.lastname: Ayroud
authors.forename: M A
authors.initials: MA
authors.lastname: VanderKop
authors.forename: D
authors.initials: D
authors.lastname: Karren
authors.forename: G S
authors.initials: GS
authors.lastname: Yost
authors.forename: K J
authors.initials: KJ
authors.lastname: Cheng
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004646:Emphysema / Q000139:chemically induced / Q000662:veterinary*; D005260:Female; D008552:Melengestrol Acetate / Q000009:adverse effects* / Q000493:pharmacokinetics; D045167:Progesterone Congeners / Q000009:adverse effects* / Q000493:pharmacokinetics; D011654:Pulmonary Edema / Q000139:chemically induced / Q000662:veterinary*; D012756:Sheep; D012757:Sheep Diseases / Q000503:physiopathology*; D012862:Skatole / Q000009:adverse effects*
chemical_list: D045167:Progesterone Congeners; D008552:Melengestrol Acetate; D012862:Skatole