The possible neuroprotective effects of melatonin in aluminum chloride-induced neurotoxicity via antioxidant pathway and Nrf2 signaling apart from metal chelation

• Published in: Environmental science and pollution research international 2019-03, Vol.26 (9), p.9174-9183
• Main Authors: Sadek, Kadry M., Lebda, Mohamed A., Abouzed, Tarek K.
• Format: Article
• Language: English
• Subjects: Aluminum; Aluminum chloride; Aluminum Chloride - toxicity; Animals; Antioxidants; Antioxidants - metabolism; Aquatic Pollution; Atmospheric Protection/Air Quality Control/Air Pollution; Biomarkers; Brain damage; Brain injury; Catalase; Catalase - genetics; Catalase - metabolism; Chelation; Chlorides; Copper; Degeneration; Earth and Environmental Science; Ecotoxicology; Environment; Environmental Chemistry; Environmental Health; Environmental science; Gene expression; Glutathione; Glutathione transferase; Homeostasis; Humans; Infiltration; Inflammation; Lipid peroxidation; Lipid Peroxidation - drug effects; Lipids; Male; Malondialdehyde; Malondialdehyde - metabolism; Melatonin; Melatonin - administration & dosage; Nervous system; Neurodegeneration; Neuroprotection; Neuroprotective Agents - administration & dosage; Neurotoxicity; Neurotoxicity Syndromes - drug therapy; Neurotoxicity Syndromes - etiology; Neurotoxicity Syndromes - genetics; Neurotoxicity Syndromes - metabolism; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; NRF2 protein; Oxidative Stress - drug effects; Peroxidation; Proteins; Rats; Rats, Wistar; Reactive oxygen species; Reactive Oxygen Species - metabolism; Research Article; Signal Transduction - drug effects; Signaling; Superoxide dismutase; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Waste Water Technology; Water Management; Water Pollution Control; Western blotting
• ISSN: 0944-1344; 1614-7499
• DOI: 10.1007/s11356-019-04430-9

Aluminum (Al) had well-identified adverse influences on the nervous system mainly through the creation of reactive oxygen species (ROS). Melatonin works as an antioxidant through the inhibition of ROS and attenuating peroxidation of lipids. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a pivotal transcription factor which controls the transcription of antioxidant enzymes. This study was conducted to determine the potential neuroprophylactic impacts of melatonin in aluminum chloride (AlCl 3 )-initiated neurotoxicity including potential mechanism(s) of action and relevant signaling in rats. Thirty-six male rats were distributed into 4 groups: Control; AlCl 3 (50 mg/kg bwt, i.p, 3 times weekly for 3 months); melatonin (5 mg/kg bwt, i.p daily for 2 weeks before AlCl 3 and sustained for the next 3 months); and melatonin with AlCl 3 . Neuronal alterations were histopathologically and biochemically evaluated. The neuronal antioxidant-related genes and relevant Nrf2 protein expression were determined by real-time PCR and Western blotting, respectively. The current data showed a substantial increase in brain damage biomarkers, acetylecholinesterase (AchE) activity, and malondialdehyde (MDA) content while the enzymatic antioxidant expression as glutathione-s-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) were substantially attenuated in the aluminum-treated group, with cleared histopathological changes as inflammatory cell infiltration with neuronal degeneration. Supplementation of melatonin resulted in an obvious amelioration in all previous abnormal alteration observed in AlCl 3 -treated rats rather than increased Al burden and/or altered Fe and Cu homeostasis with upregulating both total and phosphorylated Nrf2 expression. Therefore, the study concluded that melatonin has a potential ability to be neuroprophylactic against Al-induced neurotoxic effect and oxidative damage in the rat brain through upregulating and instigating Nrf2 signaling apart from metal chelation.