ArticleNeurotoxicity research2015
Melatonin antagonizes Mn-induced oxidative injury through the activation of keap1-Nrf2-ARE signaling pathway in the striatum of mice.
Article in Neurotoxicity research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 74 citations in OpenAlex.
- Effects of Excessive Manganese Exposure on Testicular Oxidative Stress, Histopathology, and Nrf2 Signaling Pathway in Mice.Biological trace element research · 2026Article
- Manganese modulates hepatocellular carcinoma cytotoxicity and doxorubicin sensitivity in a dose dependent manner.Frontiers in oncology · 2026Article
- Melatonin-Mediated Nrf2 Activation as a Potential Therapeutic Strategy in Mutation-Driven Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Role of manganese in brain health and disease: Focus on oxidative stress.Free radical biology & medicine · 2025Review
- Exploring melatonin's signalling pathways in the protection against age-related skin deterioration.Pharmacological reports : PR · 2025Review
- Systematic review of melatonin in cerebral ischemia-reperfusion injury: critical role and therapeutic opportunities.Frontiers in pharmacology · 2024Review
- Oxidative Stress and the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Pathway in Multiple Sclerosis: Focus on Certain Exogenous and Endogenous Nrf2 Activators and Therapeutic Plasma Exchange Modulation.International journal of molecular sciences · 2023Review
- Ultraviolet Radiation-Induced Mitochondrial Disturbances Are Attenuated by Metabolites of Melatonin in Human Epidermal Keratinocytes.Metabolites · 2023Article
- Melatonin: A Potential Regulator of DNA Methylation.Antioxidants (Basel, Switzerland) · 2023Review
- Amyotrophic Lateral Sclerosis Pathoetiology and Pathophysiology: Roles of Astrocytes, Gut Microbiome, and Muscle Interactions via the Mitochondrial Melatonergic Pathway, with Disruption by Glyphosate-Based Herbicides.International journal of molecular sciences · 2022Review
- Influence of Melatonin Treatment on Cellular Mechanisms of Redox Adaptation in K562 Erythroleukemic Cells.Genes · 2022Article
- A three-dimensional matrix system containing melatonin and neural stem cells repairs damage from traumatic brain injury in rats.Neural regeneration research · 2022Article
- A Mixture of Topical Forms of Polydeoxyribonucleotide, Vitamin C, and Niacinamide Attenuated Skin Pigmentation and Increased Skin Elasticity by Modulating Nuclear Factor Erythroid 2-like 2.Molecules (Basel, Switzerland) · 2022Article
- Melatonin Attenuates Methotrexate-Induced Reduction of Antioxidant Activity Related to Decreases of Neurogenesis in Adult Rat Hippocampus and Prefrontal Cortex.Oxidative medicine and cellular longevity · 2022Article
- Fucoxanthin Pretreatment Ameliorates Visible Light-Induced Phagocytosis Disruption of RPE Cells under a Lipid-Rich Environment via the Nrf2 Pathway.Marine drugs · 2021Article
- Effects of Daily Melatonin Supplementation on Visual Loss, Circadian Rhythms, and Hepatic Oxidative Damage in a Rodent Model of Retinitis Pigmentosa.Antioxidants (Basel, Switzerland) · 2021Article
- The potential neuroprotective effect of allicin and melatonin in acrylamide-induced brain damage in rats.Environmental science and pollution research international · 2021Article
- Melatonin Promotes In Vitro Maturation of Vitrified-Warmed Mouse Germinal Vesicle Oocytes, Potentially by Reducing Oxidative Stress through the Nrf2 Pathway.Animals : an open access journal from MDPI · 2021Article
- Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update.International journal of molecular sciences · 2021Review
- Neurotoxicity mechanisms of manganese in the central nervous system.Advances in neurotoxicology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excessive manganese (Mn) exposure can lead to oxidative injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) exerts an antioxidant response toward various environmental toxicants in the brain. However, the role of Nrf2 against Mn-induced oxidative injury remains largely unexplored. This study investigated the role of melatonin (MLT), an agent that was recently shown to induce the activation of the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2-antioxidant response elements (ARE) pathway against manganism. Mice were randomly divided into six groups, including control, 12.5, 25, 50 mg/kg MnCl2, MLT control, and MLT + 50 mg/kg MnCl2. The following were determined: behavioral activity; pathological changes; immunofluorescence staining of Neuronal Nuclei and glial fibrillary acidic protein; cell apoptosis; the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH); the immunohistochemical expression; and the protein levels of Nrf2, Keap1, and downstream enzymes. Mn-induced motor disorders, pathological damage, neuron degeneration, astrocytes activation, apoptosis, ROS and MDA generation, and GSH depletion. Nrf2, keap1, heme oxygenase-1 and NAD(P)H dehydrogenase, and quinone 1 showed a biphasic expression trend, which was most evidenced in the 12.5 mg/kg MnCl2 group. Changes in γ-glutamylcysteine synthetase, glutathione peroxidase 1, glutathionine S-transferase, glutathione reductase, and superoxide dismutase decreased in a concentration-dependent manner as a result of Mn exposure. MLT antagonized oxidative injury through the activation of the Keap1-Nrf2-ARE signaling pathway. In conclusion, disturbance of the Keap1-Nrf2-ARE signaling pathway partly caused oxidative injury. MLT can activate Nrf2 and its downstream enzymes and reverse Mn-induced oxidative injury.
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