Effects of mixed-function oxidase inducers and inhibitors on cytochrome P-450 content, gel electrophoresis profiles, and 3-methylindole-induced lung toxicity in goats.

Effects of mixed-function oxidase inducers and inhibitors on cytochrome P-450 content, gel electrophoresis profiles, and 3-methylindole-induced lung injury were studied in goats. In the first experiment, goats were pretreated with phenobarbital (PB), 3-methylindole (3MI), 3-methylcholanthrene (3MC), or SKF 525-A. Liver, lung, and kidney microsomes were used for cytochrome P-450 and gel electrophoresis studies. Although pulmonary cytochrome P-450 was not affected by any of the pretreatments, hepatic cytochrome P-450 significantly increased (P less than 0.05) after PB and 3MC pretreatment. All pretreatment resulted in changes in liver gel profiles in the 43,000 to 68,000 molecular weight region, but only PB and 3MI pretreatment altered gel profiles in the lung. In the second experiment, pretreated goats were infused with 3MI. The relative severity of lung injury in these animals, based on clinical signs, lung lesions, lung weight, and mean survival time was as follows: SKF 525-A pretreated group greater than PB-pretreated group = unpretreated group greater than 3MI-pretreated group greater than or equal to 3MC-pretreated group. The results indicate that changes in 3MI-induced lung injury are accompanied by changes in gel profiles in the molecular weight region of 43,000 to 68,000.