Depression of the Hepatic Cytochrome P‐450 Monooxygenase System by the Neurotoxin 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)

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Abstract
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 vitrostudies 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.

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