Isolation and identification of the liver microsomal cytochrome P 450 isoen zymes responsible for the formation of diazepam main metabolites nordiazepam and temazepam in rats were studied. The effects of P 450 ind...Isolation and identification of the liver microsomal cytochrome P 450 isoen zymes responsible for the formation of diazepam main metabolites nordiazepam and temazepam in rats were studied. The effects of P 450 inducers and inhibitors on the protein contents in SDS poly acrylamide gel electrophoresis and thin layer chromatography to the corresponding diazepam me tabolizing activities of rat liver microsomes were observed. The P 450 contents were dramatically re duced by ip diazepam, cimetidine or propranolol. Diazepam and propranolol inhibited temazepam formation, high dose of propranolol also inhibited nordiazepam formation. Phenobarbital increased the P 450 contents and induced the production of both nordiazepam and temazepam. It also induced proteins with molecular weight (m) of 51 and 59 kDa in SDS PAGE and those with m ranging from 45 to 55 kDa and from 55 to 65 kDa in TLC. Propranolol inhibited both fractions, especially that of m 55～65 kDa, whereas diazepam tended to inhibit the fraction of 45～55 kDa. The protein of m 51 kDa could be mainly involved in diazepam C3 hydroxylation, whereas those of m 59 kDa could be responsible for the N demethylation of diazepam in rats.展开更多
The present work aimed to demonstrate that the dietary content of the drug diazepam, a common benzodiazepine, regulates many aspect of feed efficiency of the Nile tilapia Oreochromis niloticus a favorite in fish produ...The present work aimed to demonstrate that the dietary content of the drug diazepam, a common benzodiazepine, regulates many aspect of feed efficiency of the Nile tilapia Oreochromis niloticus a favorite in fish production, and also to test introducing a simple new model in the investigation of the biological mechanisms of drug addiction. Diazepam was added to the basic diet at different levels （1.5, 3.0, 5.0, 7.0, 8.0, 9.0, 10.0, 12.0, 14.0 and 16.0 mg/100 g diet）. The experiments lasted for twelve weeks. The results obtained suggested that most of the diazepam doses were able to stimulate the growth parameters of O. niloticus, especially at 12.0 mg/100 gdiet. At some selected doses, diazepam reduces AChE specific activities in the tilapia brain and the inhibition was higher at the 12.0 mg dose. The clearance of diazepam in fish muscles and skin with lapse of time indicated that the fish treatment poses no health risk to the consumer. The recommended dose is the 12 mg DZP/100 mg diet. Finally, tilapia can be used as a new powerful model for the study of fish growth, which could provide insights into the mechanisms of drug addiction.展开更多
文摘Isolation and identification of the liver microsomal cytochrome P 450 isoen zymes responsible for the formation of diazepam main metabolites nordiazepam and temazepam in rats were studied. The effects of P 450 inducers and inhibitors on the protein contents in SDS poly acrylamide gel electrophoresis and thin layer chromatography to the corresponding diazepam me tabolizing activities of rat liver microsomes were observed. The P 450 contents were dramatically re duced by ip diazepam, cimetidine or propranolol. Diazepam and propranolol inhibited temazepam formation, high dose of propranolol also inhibited nordiazepam formation. Phenobarbital increased the P 450 contents and induced the production of both nordiazepam and temazepam. It also induced proteins with molecular weight (m) of 51 and 59 kDa in SDS PAGE and those with m ranging from 45 to 55 kDa and from 55 to 65 kDa in TLC. Propranolol inhibited both fractions, especially that of m 55～65 kDa, whereas diazepam tended to inhibit the fraction of 45～55 kDa. The protein of m 51 kDa could be mainly involved in diazepam C3 hydroxylation, whereas those of m 59 kDa could be responsible for the N demethylation of diazepam in rats.
文摘The present work aimed to demonstrate that the dietary content of the drug diazepam, a common benzodiazepine, regulates many aspect of feed efficiency of the Nile tilapia Oreochromis niloticus a favorite in fish production, and also to test introducing a simple new model in the investigation of the biological mechanisms of drug addiction. Diazepam was added to the basic diet at different levels （1.5, 3.0, 5.0, 7.0, 8.0, 9.0, 10.0, 12.0, 14.0 and 16.0 mg/100 g diet）. The experiments lasted for twelve weeks. The results obtained suggested that most of the diazepam doses were able to stimulate the growth parameters of O. niloticus, especially at 12.0 mg/100 gdiet. At some selected doses, diazepam reduces AChE specific activities in the tilapia brain and the inhibition was higher at the 12.0 mg dose. The clearance of diazepam in fish muscles and skin with lapse of time indicated that the fish treatment poses no health risk to the consumer. The recommended dose is the 12 mg DZP/100 mg diet. Finally, tilapia can be used as a new powerful model for the study of fish growth, which could provide insights into the mechanisms of drug addiction.
