DOPAMINE-DIHYDROXYPHENYLALANINE AND L-BETA-3,4-DIHYDROXYPHENYLALANINEHYDROCHLORIDE (L-DOPA)-INDUCED CYTOTOXICITY TOWARDS CATECHOLAMINERGICNEUROBLASTOMA SH-SY5Y CELLS - EFFECTS OF OXIDATIVE STRESS AND ANTIOXIDATIVE FACTORS

Enhanced oxidative stress has been suggested to be involved in the deg eneration of nigrostriatal dopaminergic neurons in Parkinson's disease . The high turnover rare of dopamine and/or unsequestered dopamine may cause an increase of formation of hydrogen peroxide via either oxidat ive deamination of dopamine by monoamine oxidase or autoxidation. Hydr ogen peroxide would be converted to more toxic hydroxyl free radicals. L-beta-3,4-Dihydroxyphenylalanine hydrochloride (L-DOPA), the most us eful drug in the symptomatic treatment of Parkinson's disease, has bee n considered to possess deteriorating degenerative side-effects. The c atecholaminergic neuroblastoma SH-SY5Y cells were chosen to investigat e the cytotoxic effect of dopamine and L-DOPA. Both dopamine and r-DOP A were found to be cytotoxic towards SH-SY5Y cells. Such toxic effects were accompanied by an increase of oxidative stress in the cell cultu res and could be reversed effectively by catalase and to a lesser exte nt by superoxide dismutase. The non-enzymatic antioxidants L-ascorbic acid, glutathione, N-acetyl-L-cysteine, bur not (+)-alpha-tocopherol, also completely protected SH-SY5Y cells against the cytotoxic effects induced by dopamine and L-DOPA. Antioxidative - factors, namely free r adical scavengers (including N-tert-butyl-alpha-phenylnitrone, salicyl ic acid, and D-mannitol) and a strong iron chelator, deferoxamine, how ever, did not protect the SH-SY5Y cells against dopamine and L-DOPA. T he generation of reactive oxygen species and the resulting enhanced ox idative stress was clearly involved in the dopamine- and L-DOPA-induce d cytotoxic effects. Hydrogen peroxide played the most important role related to cytotoxicity of dopamine and L-DOPA. Copyright (C) 1997 Els evier Science Inc.