Modification by phenobarbital of chlorphentermine-induced changes in lung morphology and drug-metabolizing enzymes in newborn rats.
Treatment of newborn rat pups with 60 mg/kg.d chlorphentermine for 7 d produced on accumulation of alveolar foam cells accompanied by an increase in relative pulmonary tissue weight. In contrast, administration of 20 mg/kg.d for 1 wk did not markedly alter lung ultrastructure or weight in newborns. Both doses of chlorphentermine elevated the activity of pulmonary aminopyrine N-demethylase but not that of aniline hydroxylase. The increase in relative liver weight was associated with stimulation of the activities of aniline hydroxylase and aminopyrine N-demethylase in newborns administered either chlorphentermine dose. Phenobarbital treatment produced an increase in relative liver weight accompanied by elevated activities of pulmonary aminopyrine N-demethylase and hepatic aniline hydroxylase and aminopyrine N-demethylase. Simultaneous barbiturate and chlorphentermine administration produced stimulation in liver enzymes to the same extent as phenobarbital alone. In contrast, phenobarbital potentiated the chlorphentermine-induced rise in pulmonary aminopyrine N-demethylase. In the case of 60 mg/kg chlorphentermine and barbiturate, the observed potentiation of lung enzyme activity was associated with a reduction in the number of alveolar foam cells. The results suggest that chlorphentermine and phenobarbital stimulate drug-metabolizing enzyme in lung and liver of newborn rats and that phenobarbital may provide protection against phospholipidosis through stimulation of pulmonary, drug-metabolizing enzymes.
D000633:Aminopyrine N-Demethylase / Q000032:analysis*; D000815:Aniline Hydroxylase / Q000032:analysis*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis*; D001835:Body Weight / Q000187:drug effects; D002745:Chlorphentermine / Q000633:toxicity*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010634:Phenobarbital / Q000494:pharmacology*; D010645:Phentermine / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains
D010645:Phentermine; D000815:Aniline Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D000633:Aminopyrine N-Demethylase; D002745:Chlorphentermine; D010634:Phenobarbital