Effect of Melatonin Administration on Mitochondrial Activity and Oxidative Stress Markers in Patients with Parkinson’s Disease

Abstract

Mitochondrial dysfunction and oxidative stress are extensively linked to Parkinson’s disease (PD) pathogenesis. Melatonin is a pleiotropic molecule with antioxidant and neuroprotective effects. The aim of this study was to evaluate the effect of melatonin on oxidative stress markers, mitochondrial complex 1 activity, and mitochondrial respiratory control ratio in patients with PD. A double-blind, cross-over, placebo-controlled randomized clinical trial study was conducted in 26 patients who received either 25 mg of melatonin or placebo at noon and 30 min before bedtime for three months. At the end of the trial, in patients who received melatonin, we detected a significant diminution of lipoperoxides, nitric oxide metabolites, and carbonyl groups in plasma samples from PD patients compared with the placebo group. Conversely, catalase activity was increased significantly in comparison with the placebo group. Compared with the placebo group, the melatonin group showed significant increases of mitochondrial complex 1 activity and respiratory control ratio. The fluidity of the membranes was similar in the melatonin group and the placebo group at baseline and after three months of treatment. In conclusion, melatonin administration was effective in reducing the levels of oxidative stress markers and restoring the rate of complex I activity and respiratory control ratio without modifying membrane fluidity. This suggests that melatonin could play a role in the treatment of PD.

Antioxidant Therapeutic Strategies in Neurodegenerative Diseases

“…From the most recent randomized clinical trials conducted in the past year and using antioxidants in neurodegenerative diseases found in this review, two of them used melatonin in different neurodegenerative contexts, including Alzheimer’s disease and Parkinson’s disease. Both of them reported interesting significant changes among groups [ 53 , 56 ], such as a significant decrease of lipoperoxides, nitric oxide metabolites, and carbonyl groups in proteins in plasma samples from patients with Parkinson’s disease receiving melatonin compared with the placebo group. Conversely, catalase activity was increased significantly in comparison with the placebo group.…”

“…Nevertheless, those reporting significant changes derived from exogenous antioxidant intake showed promising findings including changes in cognitive function and clinical prognosis [ 48 ]. Of note, some of them reported not only clinical amelioration but also improvement of molecular biomarkers, mainly mitochondrial-related activity and oxidative stress parameters [ 56 ].…”

“…The neuroprotective antioxidant effect of the hormone melatonin has been widely tested in both in vivo and in vitro studies [ 10 , 67 , 68 , 69 ]. The most recent double-blind, cross-over, placebo-controlled randomized clinical trial study using melatonin in Parkinson’s disease showed significant decreases of plasmatic levels of lipoperoxides, nitric oxide metabolites, and carbonyl groups in proteins in patients with Parkinson’s disease [ 56 ]. In contrast, catalase enzymatic activity significantly increased compared with the placebo group.…”

“…In addition, mitochondrial complex I enzymatic activity, as well as respiratory control ratio, were increased in the melatonin group, although membrane fluidity remained unaltered between groups. Although the outcomes derived from this study are restricted to a molecular level rather than reporting clinical evidence of neurocognitive improvement, taken together these molecular results suggest the effectiveness of melatonin administration in restoring mitochondrial parameters and reducing oxidative stress markers [ 56 ] ( Table 2 ).…”

Melatonin ameliorates Parkinson’s disease via regulating microglia polarization in a RORα‐dependent pathway

“…Melatonin (MLT) has proven effective as a treatment drug in PD patients and experiments with animal models also support that 14 – 16 . As an age-related hormone, MLT has been reported with broad biological effects including immunity-regulation 17 .…”