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

• DOI: 10.3892/mmr.2017.7974
• Publication Date: 2017-11-06T09:07:39Z
• Authors: Su‑Fang Zhang; Cheng‑Long Xie; Jing‑Ya Lin; Mei‑Hua Wang; Xi‑Jin Wang; Zhen‑Guo Liu
• Keywords: Dyskinesia, Drug-Induced; 0303 health sciences; Thioctic Acid; Caspase 3; Dopaminergic Neurons; Parkinson Disease; Antioxidants; Rats; 3. Good health; Levodopa; Substantia Nigra; Disease Models, Animal; Oxidative Stress; 03 medical and health sciences; Animals; Female; Poly(ADP-ribose) Polymerases; Reactive Oxygen Species

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 α‑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.