Melatonin Protects Against Titanium Oxide-Induced Neurotoxicity: Neurochemical, Neurobehavioral, and Histopathological Evidences

Sobhani, Sarvenaz; Tehrani, Ali Asghar; Sobhani, Golnar; Fatima, Sulail; Ulloa, Luis; Motaghinejad, Majid; Atif, Alina

doi:10.1007/s12011-022-03464-4

Cited by 5 publications

(2 citation statements)

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“…However, under oxidative stress, Nrf2 degradation is suppressed, allowing for its translocation to the nucleus and binding to antioxidant response element 2 (ARE) [ 28 , 29 ], which is located in the regulatory regions of genes encoding numerous antioxidant enzymes, including superoxide dismutase (Mn-SOD, Cu/Zn-SOD), catalase (CAT), γ -glutamylcysteine synthetase ( γ -GCS), heme oxygenase-1 (HO-1), NADPH quinone dehydrogenase-1 (NQO1), or glutathione peroxidase (GPx) [ 4 , 19 , 30 , 31 , 32 , 33 ]. Apart from this, melatonin affects Nrf2 via the inhibition of degradation and the promotion of its nuclear translocation [ 29 , 31 , 34 ]. Moreover, a recent in vitro study revealed that 1 nM melatonin can effectively stimulate Nrf2 via an increase in the expression levels of antioxidant and proteasome genes linked with the Keap1-Nrf2-ARE pathway [ 28 ].…”

Section: Melatonin Biosynthesis and Functionmentioning

confidence: 99%

Melatonin: A Potential Regulator of DNA Methylation

et al. 2023

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The pineal gland-derived indoleamine hormone, melatonin, regulates multiple cellular processes, ranging from chronobiology, proliferation, apoptosis, and oxidative damage to pigmentation, immune regulation, and mitochondrial metabolism. While melatonin is best known as a master regulator of the circadian rhythm, previous studies also have revealed connections between circadian cycle disruption and genomic instability, including epigenetic changes in the pattern of DNA methylation. For example, melatonin secretion is associated with differential circadian gene methylation in night shift workers and the regulation of genomic methylation during embryonic development, and there is accumulating evidence that melatonin can modify DNA methylation. Since the latter one impacts cancer initiation, and also, non-malignant diseases development, and that targeting DNA methylation has become a novel intervention target in clinical therapy, this review discusses the potential role of melatonin as an under-investigated candidate epigenetic regulator, namely by modulating DNA methylation via changes in mRNA and the protein expression of DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins. Furthermore, since melatonin may impact changes in the DNA methylation pattern, the authors of the review suggest its possible use in combination therapy with epigenetic drugs as a new anticancer strategy.

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Section: Melatonin Biosynthesis and Functionmentioning

confidence: 99%

Melatonin: A Potential Regulator of DNA Methylation

et al. 2023

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“…The role of TiO 2 NPs in the induction of neuronal cell death through oxidative stress and apoptosis has been clearly demonstrated [58], while the understanding of the participating mechanisms is evolving. The inhibitory effect of TiO 2 on hippocampal antioxidant enzymes and mitochondrial complex I, II, III, and IV activity, as well as ROS overproduction through down-regulation of Keap1 expression and subsequent Nrf2 activation, was shown to be associated with neuronal apoptosis and neuroinflammation, leading to both anxiety and motor deficits [59]. TiO 2 NP exposure also inhibited complex V activity and resulted in reduced mitochondrial ATP generation [60].…”

Section: Neuronsmentioning

confidence: 99%

From Mechanisms to Implications: Understanding the Molecular Neurotoxicity of Titanium Dioxide Nanoparticles

Aschner,

Skalny,

Santamaria

et al. 2023

Front. Biosci. (Landmark Ed)

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Titanium dioxide nanoparticles (TiO2NPs) are widely produced and used nanoparticles. Yet, TiO2NP exposure may possess toxic effects to different cells and tissues, including the brain. Recent studies significantly expanded the understanding of the molecular mechanisms underlying TiO2NP neurotoxicity implicating a number of both direct and indirect mechanisms. In view of the significant recent progress in research on TiO2NP neurotoxicity, the objective of the present study is to provide a narrative review on the molecular mechanisms involved in its neurotoxicity, with a special focus on the studies published in the last decade. The existing data demosntrate that although TiO2NP may cross blood-brain barrier and accumulate in brain, its neurotoxic effects may be mediated by systemic toxicity. In addition to neuronal damage and impaired neurogenesis, TiO2NP exposure also results in reduced neurite outgrowth and impaired neurotransmitter metabolism, especially dopamine and glutamate. TiO2NP exposure was also shown to promote α-synuclein and β-amyloid aggregation, thus increasing its toxicity. Recent findings also suggest that epigenetic effects and alterations in gut microbiota biodiversity contribute to TiO2NP neurotoxicity. Correspondingly, in vivo studies demosntrated that TiO2NPs induce a wide spectrum of adverse neurobehavioral effects, while epidemiological data are lacking. In addition, TiO2NPs were shown to promote neurotoxic effects of other toxic compounds.Here we show the contribution of a wide spectrum of molecular mechanisms to TiO2NP-induced neurotoxicity; yet, the role of TiO2NP exposure in adverse neurological outcomes in humans has yet to be fully appreciated.

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