The Janus Face of Resveratrol in Astroglial Cells

Quincozes‐Santos, André; Nardin, Patrícia; Souza, Daniela Fraga de; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca; Latini, Alexandra; Gonçalves, Carlos-Alberto; Gottfried, Carmem

doi:10.1007/s12640-009-9042-0

Cited by 46 publications

(49 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our experimental conditions, treatment of astrocytes for 3 days with low concentrations of resveratrol (from 0.1 to 10 μ M) did not induce any change in viability, whereas a toxic effect was observed when the highest concentrations of resveratrol (50 and 100 μ M) were added to cells, characterized by a dose-dependent cell mortality rate higher than 30%. These results are in accordance with those reported by Quincozes-Santos et al [47]. …”

Section: Discussionsupporting

confidence: 94%

“…Thus, they described a neuroprotective effect for low concentrations of resveratrol when high doses of this polyphenol induced cell toxicity [44–46]. Recently, Quincozes-Santos et al [47] evidenced that the nature of the stress could be more important than the resveratrol concentration. They demonstrated that under intense but short oxidative conditions resveratrol was able to protect C6 glioma cells against H 2 O 2 insult while under less intense but lasting oxidative insult, resveratrol had an opposite effect, potentiating the H 2 O 2 -induced damage and resulting in a prooxidant effect.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Specific Conditions for Resveratrol Neuroprotection against Ethanol-Induced Toxicity

Gonthier

Allibe

Cottet‐Rousselle

et al. 2012

Journal of Toxicology

View full text Add to dashboard Cite

Aims. 3,5,4′-Trihydroxy-trans-stilbene, a natural polyphenolic compound present in wine and grapes and better known as resveratrol, has free radical scavenging properties and is a potent protector against oxidative stress induced by alcohol metabolism. Today, the mechanism by which ethanol exerts its toxicity is still not well understood, but it is generally considered that free radical generation plays an important role in the appearance of structural and functional alterations in cells. The aim of this study was to evaluate the protective action of resveratrol against ethanol-induced brain cell injury. Methods. Primary cultures of rat astrocytes were exposed to ethanol, with or without a pretreatment with resveratrol. We examined the dose-dependent effects of this resveratrol pretreatment on cytotoxicity and genotoxicity induced by ethanol. Cytotoxicity was assessed using the MTT reduction test. Genotoxicity was evidenced using single cell gel electrophoresis. In addition, DNA staining with fluorescent dyes allowed visualization of nuclear damage using confocal microscopy. Results. Cell pretreatment with low concentrations of trans-resveratrol (0.1–10 μM) slowed down cell death and DNA damage induced by ethanol exposure, while higher concentrations (50–100 μM) enhanced these same effects. No protection by cis-resveratrol was observed. Conclusion. Protection offered by trans-resveratrol against ethanol-induced neurotoxicity was only effective for low concentrations of this polyphenol.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Specific Conditions for Resveratrol Neuroprotection against Ethanol-Induced Toxicity

Gonthier

Allibe

Cottet‐Rousselle

et al. 2012

Journal of Toxicology

View full text Add to dashboard Cite

show abstract

“…This cell line was originally derived from rat brain tumors and have oligodendrocytic, astrocytic and neuronal properties (Benda et al, 1968; Parker et al, 1980). C6 cells are widely used as an astrocyte-like cell line (Quincozes-Santos et al, 2009). …”

Section: Methodsmentioning

confidence: 99%

Indoxyl Sulfate Affects Glial Function Increasing Oxidative Stress and Neuroinflammation in Chronic Kidney Disease: Interaction between Astrocytes and Microglia

et al. 2017

View full text Add to dashboard Cite

Indoxyl sulfate (IS) is a protein-bound uremic toxin resulting from the metabolism of dietary tryptophan which accumulates in patients with impaired renal function, such as chronic kidney disease (CKD). IS is a well-known nephrovascular toxin but little is known about its effects on central nervous system (CNS) cells. Considering the growing interest in the field of CNS comorbidities in CKD, we studied the effect of IS on CNS cells. IS (15–60 μM) treatment in C6 astrocyte cells increased reactive oxygen species release and decreased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation, and heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 expression. Moreover, IS increased Aryl hydrocarbon Receptor (AhR) and Nuclear Factor-kB (NF-kB) activation in these cells. Similiar observations were made in primary mouse astrocytes and mixed glial cells. Inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) expression, tumor necrosis factor-α and interleukin-6 release and nitrotyrosine formation were increased by IS (15–60 μM) in primary mouse astrocytes and mixed glial cells. IS increased AhR and NF-kB nuclear translocation and reduced Nrf2 translocation and HO-1 expression in primary glial cells. In addition, IS induced cell death in neurons in a dose dependent fashion. Injection of IS (800 mg/kg, i.p.) into mice induced histological changes and increased COX-2 expression and nitrotyrosine formation in thebrain tissue. Taken together, our results show a significant contribution of IS in generating a neurotoxic enviroment and it could also have a potential role in neurodegeneration. IS could be considered also a potential therapeutical target for CKD-associated neurodegenerative complications.

show abstract

“…Following DCFH-DA exposure, the cells were scraped into phosphate-buffered saline with 0.2 % Triton X-100. The fluorescence was measured in a plate reader (Spectra Max GEMINI XPS, Molecular Devices, USA) with excitation at 485 nm and emission at 520 nm [37]. The results are expressed as percentages relative to the control conditions.…”

Section: Dcfh Oxidationmentioning

confidence: 99%

“…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]. Our group has shown that resveratrol modulates important glial functions, including glutamate uptake, glutamine synthetase (GS) activity, GSH levels and inflammatory response [22,24,[37][38][39][40]. Recently, we also demonstrated the age-related antioxidant and anti-inflammatory effects of resveratrol in hippocampal astrocytes from adult and aged Wistar rats [29].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

Self Cite

View full text Add to dashboard Cite

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.

show abstract

The Janus Face of Resveratrol in Astroglial Cells

Cited by 46 publications

References 59 publications

Specific Conditions for Resveratrol Neuroprotection against Ethanol-Induced Toxicity

Specific Conditions for Resveratrol Neuroprotection against Ethanol-Induced Toxicity

Indoxyl Sulfate Affects Glial Function Increasing Oxidative Stress and Neuroinflammation in Chronic Kidney Disease: Interaction between Astrocytes and Microglia

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

Contact Info

Product

Resources

About