Resveratrol Protects C6 Astrocyte Cell Line against Hydrogen Peroxide-Induced Oxidative Stress through Heme Oxygenase 1

Quincozes‐Santos, André; Bobermin, Larissa Daniele; Latini, Alexandra; Wajner, Moaçir; Souza, Diogo O.; Gonçalves, Carlos Alberto; Gottfried, Carmem

doi:10.1371/journal.pone.0064372

Cited by 120 publications

(79 citation statements)

References 94 publications

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“…Labeled astrocytes in these groups were large and presented with neurodegeneration-related glia activation (astrogliosis). It has been shown that astrogliosis involves an increase in size and count of astrocytes and other glia cells in affected brain regions or inflamed tissue sites and can serve as an indicator of oxidative stress [35] , which can be induced by superoxide anion [36] . GFAP immunohistochemistry in this study further showed that rats treated with NaN 3 have reactive astroglia peculiarly concentrated within the granule cell layer.…”

Section: Gbc Prevents Astrogliosis and Nf Pathology In Cerebellar Cortexmentioning

confidence: 99%

Cerebellar Molecular and Cellular Characterization in Rat Models of Alzheimer's Disease: Neuroprotective Mechanisms of Garcinia Biflavonoid Complex

et al. 2017

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Background: Recent evidences suggest that cerebellar degeneration may be associated with the development of Alzheimer's disease (AD). However, previous reports were mainly observational, lacking substantial characterization of cellular and molecular cerebellar features during AD progression. Purpose: This study is aimed at characterizing the cerebellum in rat models of AD and assessing the corresponding neuroprotective mechanisms of Garcinia biflavonoid complex (GBc). Methods: Male Wistar rats were grouped and treated alone or in combination with PBS (ad libitum)/day, corn oil (CO; 2 mL/kgBw/day), GBc (200 mg/kgBw/day), sodium azide (NaN₃) (15 mg/kgBw/day) and aluminium chloride (AlCl₃) (100 mg/kgBw/day). Groups A and B received PBS and CO, respectively; C received GBc; D received NaN₃; E received AlCl₃; F received NaN₃ then GBc subsequently; G received AlCl₃ then GBc subsequently; H received NaN₃ and GBc simultaneously while I received AlCl₃ and GBc simultaneously. Following treatments, cerebellar cortices were processed for histology, immunohistochemistry and colorimetric assays. Results: Our data revealed that cryptic granule neurons and pyknotic Purkinje cell bodies (characterized by short dendritic/axonal processes) correspond to indistinctly demarcated cerebellar layers in rats treated with AlCl₃ and NaN₃. These correlates, with observed hypertrophic astrogliosis, increased the neurofilament deposition, depleted the antioxidant system-shown by expressed superoxide dismutase and glutathione peroxidase, and cerebellar glucose bioenergetics dysfunction-exhibited in assayed lactate dehydrogenase and glucose-6-phosphate dehydrogenase. We further showed that GBc reverses cerebellar degeneration through modulation of neurochemical signaling pathways and stressor molecules that underlie AD pathogenesis. Conclusion: Cellular, molecular and metabolic neurodegeneration within the cerebellum is associated with AlCl₃ and NaN₃-induced AD while GBc significantly inhibits corresponding neurotoxicity and is more efficacious when pre-administered.

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Section: Gbc Prevents Astrogliosis and Nf Pathology In Cerebellar Cortexmentioning

confidence: 99%

Cerebellar Molecular and Cellular Characterization in Rat Models of Alzheimer's Disease: Neuroprotective Mechanisms of Garcinia Biflavonoid Complex

et al. 2017

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“…Our group has previously demonstrated the interplay between guanosine and the enzyme heme oxygenase 1 (HO-1) [12,14], which is the major enzyme responsible for the conversion of heme into CO and the antioxidant products biliverdin and bilirubin [15,16]. It has been reported that HO-1 may be a therapeutic target in the aging process and/or neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

“…It has been reported that HO-1 may be a therapeutic target in the aging process and/or neurodegenerative diseases. Increased HO-1 activity correlates with protection against stressful conditions, such as hypoxia/ ischemia, oxidative stress, and neuroinflammation [12,15,16]. Furthermore, HO-1 counteracts the transcriptional activity of nuclear factor kappa B (NFkB), which is the master regulator of oxidative stress and the inflammatory response [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Anti-aging effects of guanosine in glial cells

Souza

Bellaver

Bobermin

et al. 2016

Purinergic Signalling

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Guanosine, a guanine-based purine, has been shown to exert beneficial roles in in vitro and in vivo injury models of neural cells. Guanosine is released from astrocytes and modulates important astroglial functions, including glutamatergic metabolism, antioxidant, and anti-inflammatory activities. Astrocytes are crucial for regulating the neurotransmitter system and synaptic information processes, ionic homeostasis, energy metabolism, antioxidant defenses, and the inflammatory response. Aging is a natural process that induces numerous changes in the astrocyte functionality. Thus, the search for molecules able to reduce the glial dysfunction associated with aging may represent an approach for avoiding the onset of agerelated neurological diseases. Hence, the aim of this study was to evaluate the anti-aging effects of guanosine, using primary astrocyte cultures from newborn, adult, and aged Wistar rats. Concomitantly, we evaluated the role of heme oxygenase 1 (HO-1) in guanosine-mediated glioprotection. We observed age-dependent changes in glutamate uptake, glutamine synthetase (GS) activity, the glutathione (GSH) system, proinflammatory cytokine (tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)) release, and the transcriptional activity of nuclear factor kB (NFkB), which were prevented by guanosine in an HO-1-dependent manner. Our findings suggest guanosine to be a promising therapeutic agent able to provide glioprotection during the aging process. Thus, this study contributes to the understanding of the cellular and molecular mechanisms of guanosine in the aging process.

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“…Numerous studies ranging from cell cultures to animal models have demonstrated that resveratrol exhibits antioxidant, anti-inflammatory, anti-aging and antitumor activities [22][23][24][25][26][27][28][29][30]. Resveratrol also protects neurons and astrocytes in several neurological disease models, such as epilepsy, stroke, Alzheimer's and Parkinson's diseases [31][32][33][34][35][36].…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Protects Hippocampal Astrocytes Against LPS-Induced Neurotoxicity Through HO-1, p38 and ERK Pathways

et al. 2015

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Resveratrol, a phytoalexin found in grapes and wine, exhibits antioxidant, anti-inflammatory, anti-aging and antitumor activities. Resveratrol also protects neurons and astrocytes in several neurological disease models. Astrocytes are responsible for modulating neurotransmitter systems, synaptic information, ionic homeostasis, energy metabolism, antioxidant defense and inflammatory response. In previous work, we showed that resveratrol modulates important glial functions, including glutamate uptake, glutamine synthetase activity, glutathione (GSH) levels and inflammatory response. Furthermore, astrocytes express toll-like receptors that specifically recognize lipopolysaccharide (LPS), which has been widely used to study experimentally inflammatory response. In this sense, LPS may stimulate pro-inflammatory cytokines release and oxidative stress. Moreover, there is interplay between these signals through signaling pathways such as NFκB, HO-1 and MAPK. Thus, here, we evaluated the effects of resveratrol on LPS-stimulated inflammatory response in hippocampal primary astrocyte cultures and the putative role of HO-1, p38 and ERK pathways in the protective effect of resveratrol. LPS increased the levels of TNF-α, IL-1β, IL-6 and IL-18 and resveratrol prevented these effects. Resveratrol also prevented the oxidative and nitrosative stress induced by LPS as well as the decrease in GSH content. Additionally, we demonstrated the involvement of NFκB, HO-1, p38 and ERK signaling pathways in the protective effect of resveratrol, providing the first mechanistic explanation for these effects in hippocampal astrocytes. Our findings reinforce the neuroprotective effects of resveratrol, which are mainly associated with anti-inflammatory and antioxidant activities.

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Resveratrol Protects C6 Astrocyte Cell Line against Hydrogen Peroxide-Induced Oxidative Stress through Heme Oxygenase 1

Cited by 120 publications

References 94 publications

Cerebellar Molecular and Cellular Characterization in Rat Models of Alzheimer's Disease: Neuroprotective Mechanisms of <b><i>Garcinia</i></b> Biflavonoid Complex

Cerebellar Molecular and Cellular Characterization in Rat Models of Alzheimer's Disease: Neuroprotective Mechanisms of <b><i>Garcinia</i></b> Biflavonoid Complex

Anti-aging effects of guanosine in glial cells

Resveratrol Protects Hippocampal Astrocytes Against LPS-Induced Neurotoxicity Through HO-1, p38 and ERK Pathways

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