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Protective Effect of Harmalol and Harmaline on MPTP Neurotoxicity in the Mouse and Dopamine‐Induced Damage of Brain Mitochondria and PC12 Cells
Author(s) -
Lee Chung Soo,
Han Eun Sook,
Jang Yoon Young,
Han Jeong Ho,
Ha Hyun Wook,
Kim Doo Eung
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0750521.x
Subject(s) - harmaline , mptp , chemistry , harmine , dopamine , neurotoxicity , monoamine oxidase , pharmacology , glutathione peroxidase , superoxide dismutase , biochemistry , glutathione , rotenone , mitochondrion , oxidative stress , endocrinology , biology , toxicity , dopaminergic , enzyme , organic chemistry
The present study elucidated the protective effect of β‐carbolines (harmaline, harmalol, and harmine) on oxidative neuronal damage. MPTP treatment increased activities of total superoxide dismutase, catalase, and glutathione peroxidase and levels of malondialdehyde and carbonyls in the basal ganglia, diencephalon plus midbrain of brain compared with control mouse brain. Coadministration of harmalol (48 mg/kg) attenuated the MPTP effect on the enzyme activities and formation of tissue peroxidation products. Harmaline, harmalol, and harmine attenuated both the 500 μ M MPP + ‐induced inhibition of electron flow and membrane potential formation and the 100 μ M dopamine‐induced thiol oxidation and carbonyl formation in mitochondria. The scavenging action of β‐carbolines on hydroxyl radicals was represented by inhibition of 2‐deoxy‐ d ‐ribose degradation. Harmaline and harmalol (100 μ M ) attenuated 200 μ M dopamine‐induced viability loss in PC12 cells. The β‐carbolines (50 μ M ) attenuated 50 μ M dopamine‐induced apoptosis in PC12 cells. The compounds alone did not exhibit significant cytotoxic effects. The results indicate that β‐carbolines attenuate brain damage in mice treated with MPTP and MPP + ‐induced mitochondrial damage. The compounds may prevent dopamine‐induced mitochondrial damage and PC12 cell death through a scavenging action on reactive oxygen species and inhibition of monoamine oxidase and thiol oxidation.