Protective effect of harmalol and harmaline on MPTP neurotoxicity in the mouse and dopamine-induced damage of brain mitochondria and PC12 cells

The present study elucidated the protective effect of beta-carbolines (harm aline, harmalol, and harmine) on oxidative neuronal damage. MPTP treatment increased activities of total superoxide dismutase, catalase, and glutathio ne peroxidase and levels of malondialdehyde and carbonyls in the basal gang lia, 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 mu M MPP+- induced inhibitio n of electron flow and membrane potential formation and the 100 mu M dopami ne-induced thiol oxidation and carbonyl formation in mitochondria. The scav enging action of beta-carbolines on hydroxyl radicals was represented by in hibition of 2-deoxy-o-ribose degradation. Harmaline and harmalol (100 mu M) attenuated 200 mu M dopamine-induced viability loss in PC12 cells. The bet a-carbolines (50 mu M) attenuated 50 mu M dopamine-induced apoptosis in PC1 2 cells. The compounds alone did not exhibit significant cytotoxic effects. The results indicate that beta-carbolines attenuate brain damage in mice t reated with MPTP and MPP+-induced mitochondrial damage, The compounds may p revent dopamine-induced mitochondrial damage and PC12 cell death through a scavenging action on reactive oxygen species and inhibition of monoamine ox idase and thiol oxidation.