Caffeine and uric acid mediate glutathione synthesis for neuroprotection

Aoyama, Koji; Matsumura, Nobuko; Watabe, Masahiko; Wang, F.; Kikuchi-Utsumi, Kazue; Nakaki, Toshio

doi:10.1016/j.neuroscience.2011.02.047

Cited by 73 publications

(52 citation statements)

References 45 publications

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“…Given that cysteine is the limiting amino acid for the glutathione synthesis (Chung et al 1990) and caffeine may stimulate the cysteine uptake by cells (Aoyama et al 2011), probably the GSH/GSSG ratio was improved, at least partially, by this mechanism. After subchronic caffeine administration in ovariectomized rats, the GSH/GSSG ratios in blood and brain increased, close to control levels.…”

Section: Discussionmentioning

confidence: 99%

Modulatory effects of caffeine on oxidative stress and anxiety-like behavior in ovariectomized rats

Caravan

Berghian

Moldovan

et al. 2016

Can. J. Physiol. Pharmacol.

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Menopause is accompanied by enhanced oxidative stress and behavioral changes, effects attenuated by antioxidants. The aim of this study was to evaluate the effects of caffeine on behavior and oxidative stress in an experimental model of menopause. Female rats were divided in: sham-operated (CON), sham-operated and caffeine-treated (CAF), ovariectomized (OVX), ovariectomized and caffeinetreated (OVX+CAF). Caffeine (6 mg/kg) and vehicle were administered for 21 days (subchronic) and 42 days (chronic), using 2 experimental subsets. Behavioral tests and oxidative stress parameters in the blood, whole brain and hippocampus were assessed. The subchronic administration of caffeine decreased the lipid peroxidation and improved the antioxidant defense in the blood and brain. The GSH/GGSG ratio in the brain was improved by chronic administration, with reduced activities of antioxidant enzymes and enhanced nitric oxide and malondialdehyde levels. In particular, the lipid peroxidation in the hippocampus decreased in both experiments. The rats became hyperactive after 21 days of treatment, but no effect was observed after chronic administration. In both experimental subsets, caffeine had anxiolytic effects as tested in EPM. The administration of low doses of caffeine, for a short period of time, may be a new therapeutic approach to modulating the oxidative stress and anxiety in menopause.

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Section: Discussionmentioning

confidence: 99%

Modulatory effects of caffeine on oxidative stress and anxiety-like behavior in ovariectomized rats

Caravan

Berghian

Moldovan

et al. 2016

Can. J. Physiol. Pharmacol.

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“…Urate administration similarly showed benefit in spinal cord injury models by protecting against glutamate toxicity and secondary damage including lipid peroxidation, activation of poly(ADP-ribose) polymerase and general tissue damage (213, 214). Intraperitoneal urate therapy given to mice resulted in increased glutathione production in the hippocampal CA1 pyramidal neurons in slice culture, protecting these cells from oxidative stress (215). …”

Section: Urate In Cellular and Animal Models Of Pdmentioning

confidence: 99%

Targeting urate to reduce oxidative stress in Parkinson disease

Crotty

Ascherio

Schwarzschild

2017

Experimental Neurology

112

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Oxidative stress has been implicated as a core contributor to the initiation and progression of multiple neurological diseases. Genetic and environmental factors can produce oxidative stress through mitochondrial dysfunction leading to the degeneration of dopaminergic and other neurons underlying Parkinson disease (PD). Although clinical trials of antioxidants have thus far failed to demonstrate slowed progression of PD, oxidative stress remains a compelling target. Rather than prompting abandonment of antioxidant strategies, these failures have raised the bar for justifying drug and dosing selections and for improving study designs to test for disease modification by antioxidants. Urate, the main antioxidant found in plasma as well as the end product of purine metabolism in humans, has emerged as a promising potential neuroprotectant with advantages that distinguish it from previously tested antioxidant agents. Uniquely, higher urate levels in plasma or cerebrospinal fluid (CSF) have been linked to both a lower risk of developing PD and to a slower rate of its subsequent progression in numerous large prospective epidemiological and clinical cohorts. Laboratory evidence that urate confers neuroprotection in cellular and animal models of PD, possibly via the Nrf2 antioxidant response pathway, further strengthened its candidacy for rapid clinical translation. An early phase trial of the urate precursor inosine demonstrated its capacity to safely produce well tolerated, long-term elevation of plasma and CSF urate in early PD, supporting a phase 3 trial now underway to determine whether oral inosine dosed to elevate urate to concentrations predictive of favorable prognosis in PD slows clinical decline in people recently diagnosed, dopamine transporter-deficient PD.

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“…Although most of the neuroprotective effects of caffeine have been attributed to the blockade of adenosine receptors (Chen et al 2001;Dall 0 Igna et al 2003Arendash et al 2006;Canas et al 2009), recent evidence suggests that caffeine may also promotes neuroprotection by inducing neuronal glutathione synthesis, one of the major free radical scavengers in the brain (Aoyama et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of White Tea Against Oxidative Stress-Induced Toxicity in Striatal Cells

2011

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Tea is one of the most widely consumed beverages in the world and represents an important source of antioxidants mainly catechins that confer beneficial effects in reducing the risk of cardiovascular diseases, age-related disorders or cancer. In the central nervous system, oxidative stress caused by increased production of reactive oxygen and nitrogen species represents an important mechanism for neuronal dysfunction and cell loss in different neurodegenerative disorders. The neuroprotective effects of green-tea-derived polyphenols have extensively been demonstrated in different models of neurotoxicity. However, few data have been reported on the antioxidant activity of white tea extracts in the nervous system. In the present study, we demonstrate that white tea extracts protect striatal cell lines against oxidative stress-mediated cell death. The effects of white tea on protection of striatal cell cultures are likely associated with the antioxidant properties of white tea components since neuronal cell loss induced by nonoxidative insults such as D1 dopamine receptor activation cannot be prevented by pre-treatment with white tea. Altogether our results suggest that regular consumption of white tea may contribute to reduce oxidative stress associated with brain injury and be clinically useful for treating age-related and neurodegenerative disorders.

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Caffeine and uric acid mediate glutathione synthesis for neuroprotection

Cited by 73 publications

References 45 publications

Modulatory effects of caffeine on oxidative stress and anxiety-like behavior in ovariectomized rats

Modulatory effects of caffeine on oxidative stress and anxiety-like behavior in ovariectomized rats

Targeting urate to reduce oxidative stress in Parkinson disease

Neuroprotective Effects of White Tea Against Oxidative Stress-Induced Toxicity in Striatal Cells

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