Alpha-lipoic acid protects against 6-hydroxydopamine-induced neurotoxicity in a rat model of hemi-parkinsonism

Parkinson's disease (PD) is a progressive and debilitating neurodegenerative disorder for which current treatments afford symptomatic relief with no prevention of disease progression. Due to the neuroprotective and anti-apoptotic potential of alpha lipoic acid (LA), this study was undertaken to evaluate whether LA could improve behavioral and cellular abnormalities and markers of oxidative stress in an experimental model of early PD in rat. Unilateral intrastriatal 6-hydroxydopamine (6-OHDA)-lesioned rats were pretreated p.o. with LA at doses of 50 and/or 100 mg/kg twice at an interval of 24 h. After 1 week, apomorphine caused significant contralateral rotations, a significant reduction in the number of neurons was observed on the left side of the substantia nigra pars compacta (SNC), and malondialdehyde (MDA) and nitrite levels in midbrain homogenate significantly increased and activity of superoxide dismutase significantly reduced in the 6-OHDA group. LA pretreatment at a dose of 100 mg/kg significantly attenuated rotations, prevented loss of SNC neurons, and lowered levels of MDA and nitrite. These results suggest that LA could partially afford neuroprotection against 6-OHDA neurotoxicity that is in part due to the attenuation of oxidative stress burden and this may provide benefits, along with other therapies, in neurodegenerative disorders including PD.

► Apomorphine caused contralateral rotations in the 6-OHDA group.
► A reduction in the number of SNC neurons was observed.
► MDA and nitrite levels increased and activity of superoxide dismutase reduced.
► Lipoic acid improved turning behavior and prevented loss of SNC neurons.
► Lipoic acid pretreatment lowered levels of MDA and nitrite.