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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.

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Sulfite, commonly used as a preservative in foods, beverages, and pharmaceuticals, is a very reactive and potentially toxic molecule which is detoxified by sulfite oxidase (SOX). Changes induced by aging may be exacerbated by exogenous chemicals like sulfite. The aim of this study was to investigate the effects of ingested sulfite on visual evoked potentials (VEPs) and brain antioxidant statuses by measuring superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. Brain lipid oxidation status was also determined via thiobarbituric acid reactive substances (TBARS) in normal- and SOX-deficient aged rats. Rats do not mimic the sulfite responses seen in humans because of their relatively high SOX activity level. Therefore this study used SOX-deficient rats since they are more appropriate models for studying sulfite toxicity. Forty male Wistar rats aged 24 months were randomly assigned to four groups: control (C), sulfite (S), SOX-deficient (D) and SOX-deficient + sulfite (DS). SOX deficiency was established by feeding rats with low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg kg(-1) day(-1)) was given by gavage. Treatment continued for 6 weeks. At the end of the experimental period, flash VEPs were recorded. Hepatic SOX activity was measured to confirm SOX deficiency. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with the normal rats. The activity of SOX in deficient rats was thus in the range of humans. There was no significant difference between control and treated groups in either latence or amplitude of VEP components. Brain SOD, CAT, and GPx activities and brain TBARS levels were similar in all experimental groups compared with the control group. Our results indicate that exogenous administration of sulfite does not affect VEP components and the antioxidant/oxidant status of aged rat brains.

Introduction. Docosahexaenoic acid (DHA) has been shown to have beneficial effects on Parkinson's disease (PD). The aim of this study was to investigate if the DHA acts on neurons of substantia nigra (SN) by phosphorylation of neuronal nitric oxide synthase (nNOS) in an experimental mouse model of PD. Material and methods. An experimental model of PD was created by intraperitoneal injections (4 × 20 mg/kg) of the neurotoxin 1-methyl-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Three-month-old male C57BL/6 mice were randomly divided into four groups as follows: control (C), DHA-treated (DHA), MPTP-injected (MPTP) and DHA-treated and MPTP-injected (DHA + MPTP). DHA (36 mg/kg/day) was administered daily by gavage for four weeks. Motor activity of the mice was evaluated with pole, locomotor activity and rotarod tests. Caspase-3 activity, nitrate/nitrite and 4-hydroxynonenal (4-HNE) levels were determined by spectrophotometric assays. Immunohistochemistry was used to localize and assess the expressions of tyrosine hydroxylase (TH), nNOS and phospho-nNOS (p-nNOS) in SN.Results. An increased return and total down time in the MPTP group was observed in the pole test, while DHA treatment decreased both parameters. The ambulatory activity, total distance and total locomotor activities were decreased in the MPTP group, whereas they were increased by DHA treatment. MPTP-treated animals exhibited shorter time on the rod test which was significantly increased by DHA treatment. DHA administration significantly decreased 4-HNE and nitrate/nitrite levels of SN supernatants and protected the TH (+) dopaminergic neurons of SN in the DHA + MPTP group compared to the MPTP group. DHA treatment significantly decreased nNOS and increased p-nNOS immunoreactivities in the DHA + MPTP group compared to the MPTP group. Conclusions. These results indicate that DHA treatment protects dopaminergic neurons in SN via increasing nNOS serine 852 phosphorylation in the experimental mice model of PD.