Melatonin and its metabolites as chemical agents capable of directly repairing oxidized DNA

Pérez-González, Adriana; Castañeda‐Arriaga, Romina; Álvarez-Idaboy, J. Raúl; Reíter, Russel J.; Galano, Annia

doi:10.1111/jpi.12539

Cited by 38 publications

(31 citation statements)

References 147 publications

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“…Indeed, several previous studies have shown that MLT may induce antioxidase activity, increase nonenzymatic antioxidant GSH, and decrease subsequent oxidative damage . Besides MLT itself, its metabolites are also known to exert protective effects against oxidative damage . Therefore, the antioxidant protection offered by melatonin in the present study may be a collective effect of both the parent molecule and its metabolites …”

Section: Discussionmentioning

confidence: 61%

Melatonin alleviates cognition impairment by antagonizing brain insulin resistance in aged rats fed a high‐fat diet

Gao

Zhang

et al. 2019

Journal of Pineal Research

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Brain insulin resistance, induced by neuroinflammation and oxidative stress, contributes to neurodegeneration, that is, processes that are associated with Aβ accumulation and TAU hyperphosphorylation. Here, we tested the effect of chronic administration of melatonin (MLT) on brain insulin resistance and cognition deficits caused by a high-fat diet (HFD) in aged rats. Results showed that MLT supplementation attenuated peripheral insulin resistance and lowered hippocampal oxidative stress levels.Activated microglia and astrocytes and hippocampal levels of TNF-α in HFD-fed rats were reduced by MLT treatment. Melatonin also prevented HFD-induced increases in beta-amyloid (Aβ) accumulation and TAU phosphorylation in the hippocampus. In addition, impairments of brain insulin signaling elicited by long-term HFD were restored by MLT treatment, as confirmed by ex vivo insulin stimulation.Importantly, MLT reversed HFD-induced cognitive decline as measured by a water maze test, normalized hippocampal LTP and restored CREB activity and BDNF levels as well as cholinergic neuronal activity in the hippocampus. Collectively, these findings indicate that MLT may exhibit substantial protective effects on cognition, via restoration of brain insulin signaling. K E Y W O R D Samyloid-β, brain insulin resistance, cognition impairment, melatonin, neuroinflammation, oxidative stress, TAU phosphorylation 2 of 14 | XU et al. How to cite this article: Xu J, Gao H, Zhang L, et al. Melatonin alleviates cognition impairment by antagonizing brain insulin resistance in aged rats fed a high-fat diet. J Pineal Res. 2019;67:e12584. https ://doi.

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Section: Discussionmentioning

confidence: 61%

Melatonin alleviates cognition impairment by antagonizing brain insulin resistance in aged rats fed a high‐fat diet

Gao

Zhang

et al. 2019

Journal of Pineal Research

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“…Oxidative stress has been proven to decrease Δψm, resulting in increased apoptosis in bovine oocytes [33] and human sperm [34,35]. Therefore, lower levels of ROS (Figure 1B), higher levels of endogenous antioxidants (Figure 1C) in the melatonin groups and the capability of melatonin and its metabolities in directly repairing oxidized DNA [36] explained the lower percentage of early necrotic sperm (Figure 2) and higher Δψm sperm percentage (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

Melatonin Improves the Fertilization Capacity of Sex-Sorted Bull Sperm by Inhibiting Apoptosis and Increasing Fertilization Capacitation via MT1

Hao

Zhao

et al. 2019

IJMS

Self Cite

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Little information is available regarding the effect of melatonin on the quality and fertilization capability of sex-sorted bull sperm, and even less about the associated mechanism. Sex-sorted sperm from three individual bulls were washed twice in wash medium and incubated in a fertilization medium for 1.5 h, and each was supplemented with melatonin (0, 10−3 M, 10−5 M, 10−7 M, and 10−9 M). The reactive oxygen species (ROS) and endogenous antioxidant activity (glutathione peroxidase (GPx); superoxide dismutase (SOD); catalase (CAT)), apoptosis (phosphatidylserine [PS] externalization; mitochondrial membrane potential (Δψm)), acrosomal integrity events (malondialdehyde (MDA) level; acrosomal integrity), capacitation (calcium ion [Ca2+]i level; cyclic adenosine monophosphate (cAMP); capacitation level), and fertilization ability of the sperm were assessed. Melatonin receptor 1 (MT1) and 2 (MT2) expression were examined to investigate the involvement of melatonin receptors on sex-sorted bull sperm capacitation. Our results show that treatment with 10−5 M melatonin significantly decreased the ROS level and increased the GPx, SOD, and CAT activities of sex-sorted bull sperm, which inhibited PS externalization and MDA levels, and improved Δψm, acrosomal integrity, and fertilization ability. Further experiments showed that melatonin regulates sperm capacitation via MT1. These findings contribute to improving the fertilization capacity of sex-sorted bull sperm and exploring the associated mechanism.

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“…59 For example, in sepsis-related myocardial injury, LPS promotes cardiomyocyte death and mitochondrial dysfunction via the Drp1/F-actin signaling pathway. 60 Besides, LPS also modulates the metabolism and viability of SH-SY5Y cells in the presence of BV-2 microglia. Moreover, pro-inflammatory macrophages are activated by LPS via the PARP1-LSD1 axis under oxidative conditions.…”

Section: Discussionmentioning

confidence: 99%

TrxR2 overexpression alleviates inflammation-mediated neuronal death via reducing the oxidative stress and activating the Akt–Parkin pathway

Gao¹,

Li²,

Li³

et al. 2019

Toxicology Research

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Neuronal death caused by inflammatory cytokine-mediated neuroinflammation is being extensively explored. Thioredoxin reductase (TrxR) 2 is a novel mediator of inflammation response. In the current study, we focus on the mechanisms of TrxR2 overexpression in inflammation-mediated neuronal death. LPS was used to induce neuroinflammation in N2a cells in vitro. Adenovirus-loaded TrxR2 was transfected into N2a cells to up-regulate TrxR2 expression. Then, cell viability was determined via MTT assay and TUNEL assay. Apoptosis was measured via western blotting and ELISA. Oxidative stress was detected via ELISA and flow cytometry. A pathway inhibitor was used to verify the role of the Akt–Parkin pathway in the LPS-mediated N2a cell death in the presence of TrxR2 overexpression. With the help of immunofluorescence assay and western blotting, we found that TrxR2 expression was significantly reduced in response to LPS treatment, and this effect was associated with N2a cell death via apoptosis. At the molecular level, TrxR2 overexpression elevated the activity of the Akt–Parkin pathway, as evidenced by the increased expression of p-Akt and Parkin. Interestingly, inhibition of the Akt–Parkin pathway abolished the regulatory effect of TrxR2 on LPS-treated N2a cells, as evidenced by the decreased cell viability and increased apoptotic ratio. Besides, TrxR2 overexpression also reduced oxidative stress, inflammation factor transcription and mitochondrial apoptosis. However, inhibition of Akt–Parkin axis abrogated the protective effects of TrxR2 on redox balance, mitochondrial performance and cell survival. LPS-mediated neuronal death was linked to a drop in TrxR2 overexpression and the inactivation of the Akt–Parkin pathway. Overexpression of TrxR2 sustained mitochondrial function, inhibited oxidative stress, repressed inflammation response, and blocked mitochondrial apoptosis, finally sending a pro-survival signal for the N2a cells in the setting of LPS-mediated inflammation environment.

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Melatonin and its metabolites as chemical agents capable of directly repairing oxidized DNA

Cited by 38 publications

References 147 publications

Melatonin alleviates cognition impairment by antagonizing brain insulin resistance in aged rats fed a high‐fat diet

Melatonin alleviates cognition impairment by antagonizing brain insulin resistance in aged rats fed a high‐fat diet

Melatonin Improves the Fertilization Capacity of Sex-Sorted Bull Sperm by Inhibiting Apoptosis and Increasing Fertilization Capacitation via MT1

TrxR2 overexpression alleviates inflammation-mediated neuronal death via reducing the oxidative stress and activating the Akt–Parkin pathway

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