Melatonin is protective against 6-hydroxydopamine-induced oxidative stress in a hemiparkinsonian rat model

Abstract

Melatonin is known to reduce detrimental effects of free radicals by stimulating antioxidant enzymes; however, its role has not been studied in 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease (PD). Therefore, we aimed to elucidate the effects of melatonin on motor activity and oxidative stress parameters in 6-OHDA-induced rat model of PD. Three-month-old male Wistar rats were divided into 5 groups: vehicle (V), melatonin-treated (M), 6-OHDA-injected (6-OHDA), 6-OHDA-injected + melatonin-treated (6-OHDA-Mel), and melatonin-treated + 6-OHDA-injected (Mel-6-OHDA) group. Melatonin was administered intraperitoneally at a dose of 10 mg/kg/day for 30 days in M and Mel-6-OHDA groups, for 7 days in 6-OHDA-Mel group. Rats received a unilateral stereotaxic injection of 6-OHDA into the right medial forebrain bundle. The 6-OHDA-Mel group started receiving melatonin when experimental PD was created and the treatment was continued for 7 days. In the Mel-6-OHDA group, experimental PD was created on the 23rd day of melatonin treatment and continued for the remaining 7 days. Locomotor activity decreased in 6-OHDA group compared with that in vehicle group; however, melatonin treatment did not improve this impairment. 6-OHDA injection caused an obvious reduction in tyrosine-hydroxylase-positive dopaminergic neuron viability as determined by immunohistochemistry. Melatonin supplementation decreased dopaminergic neuron death in 6-OHDA-Mel and Mel-6-OHDA groups compared with that in 6-OHDA group. Biochemical analysis confirmed the beneficial effects of melatonin displaying higher superoxide dismutase, catalase, and glutathione peroxidase activities and lower lipid peroxidation in substantia nigra samples in comparison to non-treated 6-OHDA group. Starting melatonin treatment before creating experimental PD was more effective on observed changes.

Serum uric acid levels in patients with Parkinson’s disease: A meta-analysis

“…But increasing evidence suggests that an oxidative stress plays an important role in the degeneration of dopaminergic neurons in PD[3]. Consequently, research efforts have been directed towards understanding the pathological role of oxidative stress in the pathogenesis and in the hope of developing more effective therapy approaches for the treatment of PD[4]. …”

<p>Neuroprotective effect and mechanism of baicalin on Parkinson’s disease model induced by 6-OHDA</p>

“…Therefore, 6-OHDA-induced PD model rats were used to explore the therapeutic effect and main mechanism of baicalin. [25][26][27] Our study found that when DA neurons were impaired in the SN and striatum of PD patients, the movement of PD DA synthesized by DA neurons is mainly transported via axons to the striatum. DA is an important monoamine neurotransmitter in the brain and PD dyskinesia correlated with DA levels.…”

Circadian rhythms, Neuroinflammation and Oxidative Stress in the Story of Parkinson’s Disease

“…GSH expression, and GSSG/GSH ratio are increased after melatonin administration in the rat model of PD [74]. Malondialdehyde (MDA) expression, a marker of oxidative stress, is decreased while SOD is increased under melatonin administration in rat model of PD induced by 6-OHDA or by MPTP [75]. In the same way, other models of PD rats induced by rotenone have shown the increase of both GSH and SOD after melatonin administration [76].…”