EFFECT OF MELENGESTROL ACETATE ON DEVELOPMENT OF 3-METHYLINDOLE-INDUCED PULMONARY-EDEMA AND EMPHYSEMA IN SHEEP

The involvement of melengestrol acetate (MGA) in susceptibility to dev eloping 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 wer e 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 e arlier (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 concentratio ns did not differ between treatments (P > 0.05). Ewes receiving MGA ha d higher (P < 0.05) concentrations of 3MI metabolites in plasma prior to dosing than did control ewes, and these values tended to remain hig her throughout the sampling period. Immunoreactivity assays indicated more pneumotoxin present in the lungs of MGA-treated ewes than control s. Lung damage was apparently more acute and accelerated in the MGA-tr eated ewes than in the controls. Urinary 3MI mercapturate concentratio ns 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 thes e findings for MGA-treated feedlot heifers are currently under investi gation.