Depression of the hepatic cytochrome P-450 monooxygenase system by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
The effects of the neurotoxic compound, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the hepatic cytochrome P-450 monooxygenase system were assessed using C57 BL/6J mice. Treatment with MPTP caused a marked depression of hepatic cytochrome P-450 content, ethoxyresorufin O-dealkylase and NADPH cytochrome C reductase activities. This effect was maximal 3 to 6 hours after treatment and was dependent on the dose of MPTP administered. Depression of spectrophotometrically measured cytochrome P-450 content was associated with increase in cytochrome P-420 content and lipid peroxidation. In vitro studies showed the formation of a metabolic-intermediate complex with cytochrome P-450 which may partially explain the depression of cytochrome P-450 content and activity by MPTP.
Shahi
G S
GS
Department of Physiology, National University of Singapore.
Moochhala
S M
SM
Das
N P
NP
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000201:enzymology*; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D013997:Time Factors
D065607:Cytochrome P-450 Enzyme Inhibitors; D011725:Pyridines; D003577:Cytochrome P-450 Enzyme System; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D010105:Oxygenases