Protective effect of boldine on dopamine-induced membrane permeability transition in brain mitochondria and viability loss in PC12 cells.

Boldine ([S]-2,9-dihydroxy-1,10-dimethoxyaporphine) has been shown to exert antioxidant and anti-inflammatory effects. The present study elucidated the protective effect of boldine on catecholamine-induced membrane permeability transition in brain mitochondria and viability loss in PC12 cells. Dopamine (200 microM) and 6-hydroxydopamine (6-OHDA, 100 microM) attenuated Ca(2+) and succinate-induced mitochondrial swelling and membrane potential formation. Boldine (10-100 microM) and 10 microg/mL of superoxide dismutase (SOD) or catalase reduced the effect of catecholamine oxidation on brain mitochondria. Boldine, SOD, and catalase decreased catecholamine-induced mitochondrial cytochrome c release. Antioxidant enzymes attenuated the depressant effect of catecholamines on mitochondrial electron flow, whereas boldine did not reduce it. Boldine inhibited the catecholamine-induced decrease in thioredoxin reductase activity and the increase in thiol oxidation in mitochondria. It also showed a scavenging action on hydrogen peroxide and hydroxyl radicals and decreased the formation of melanin from dopamine. Boldine and antioxidant enzymes decreased the dopamine-induced cell death, including apoptosis, in PC12 cells. The results suggest that boldine may attenuate the catecholamine oxidation-induced brain mitochondrial dysfunction and decrease the dopamine-induced death of PC12 cells through a scavenging action on reactive oxygen species and inhibition of melanin formation and thiol oxidation.