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|Title:||Loss of cytochrome P-450 monooxygenase activity and formation of a metabolic-intermediate complex after administration of the neurotoxin MPTP to C57 BL/6J mice|
|Authors:||Shahi, G.S. |
|Citation:||Shahi, G.S., Das, N.P., Moochhala, S.M. (1989). Loss of cytochrome P-450 monooxygenase activity and formation of a metabolic-intermediate complex after administration of the neurotoxin MPTP to C57 BL/6J mice. Asia Pacific Journal of Pharmacology 4 (2) : 89-94. ScholarBank@NUS Repository.|
|Abstract:||The in vivo effects of MPTP on hepatic cytochrome P-450 enzyme activity were studied in relation to the formation of a metabolic-intermediate complex on interaction of MPTP with the hepatic cytochrome P-450 enzyme system in untreated, phenobarbitone (PB)- and β-naphthoflavone (BNF)-pretreated C57BL/6J mice. MPTP depressed cytochrome P-450 monooxygenase activity in general and was found to selectively depress pentoxyresorufin O-dealkylase (PROD) activity in comparison to its effect on ethoxyresorufin O-dealkylase (EROD) activity. MPTP treatment also resulted in a loss of measurable cytochrome P-450 level in non-induced (reduced to 37% of level in non-MPTP treated mice), PB-induced (reduced to 40%) and BNF-induced microsomes (57%). Ferricyanide dissociation studies suggest that in vivo complex formation accounts for some (but not all) of this loss in non-induced (17%) PB-induced (10%) and BNF-induced microsomes (7%). Other possible mechanisms for the loss of cytochrome P-450 which may be involved, such as the conversion of cytochrome P-450 to P-420 and free radical-related damage are also discussed.|
|Source Title:||Asia Pacific Journal of Pharmacology|
|Appears in Collections:||Staff Publications|
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