Lipoic acid alleviates L‑DOPA‑induced dyskinesia in 6‑OHDA parkinsonian rats via anti‑oxidative stress.

Levodopa (L-DOPA) is the gold standard for symptomatic treatment of Parkinson's disease (PD); however, long-term therapy is associated with the emergence of L-DOPA-induced dyskinesia (LID). Nigral dopaminergic cell loss determines the degree of drug exposure and time required for the initial onset of LID. Accumulating evidence indicates that -lipoic acid (ALA) decreases this nigral dopaminergic cell loss. However, until now, the precise mechanisms of ALA have only been partially understood in LID. Chronic L-DOPA treatment was demonstrated to develop intense AIM scores to assess dyskinetic symptoms. Rats in the LID group were administrated twice daily with L-DOPA + benserazide for 3 weeks to induce a rat model of dyskinesia. Moreover, other 6-OHDA-lesioned rats were treatment with ALA (31.5 mg/kg or 63 mg/kg) in combination with L-DOPA treatment. Furthermore, the authors investigated the level of malondialdehyde (MDA) and glutathione (GSH) activity, as well as IBa-1, caspase-3 and poly (ADP-ribose) polymerase (PARP) in substantia nigra by the way of western blotting and immunofluorescence. ALA reduced LID in a dose-dependent manner without compromising the anti-PD effect of L-DOPA. Moreover, ALA reduced the level of MDA and upregulated the GSH activity, as well as ameliorated IBa-1 positive neurons in the substantia nigra. Finally, it was identified that ALA could reduce L-DOPA-induced cleaved-caspase-3 and PARP overexpression in the substantia nigra. Based on the present findings, ALA could be recommended as a promising disease-modifying therapy when administered with L-DOPA early in the course of PD. The exact mechanism for this action, although incompletely understood, appears to relate to anti-oxidative stress and anti-apoptosis.