Polyols accumulated in ribose‐5‐phosphate isomerase deficiency increase mitochondrial superoxide production and improve antioxidant defenses in rats' prefrontal cortex

Stone, Vinícius; Kudo, Karen Yurika; August, Pauline Maciel; Marcelino, Thiago Beltram; Matté, Cristiane

doi:10.1016/j.ijdevneu.2014.06.009

Cited by 10 publications

(5 citation statements)

References 28 publications

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“…Another interesting finding of our study is that ribitol treatment, again in contrast to ribose treatment, significantly increases levels of reduced glutathione (GSH). This result is in agreement with an early report by Stone et al in 2014 [ 35 ]. The previous study aimed to assess the roles of polyols, specifically arabitol and ribitol, in the pathophysiology of a disease caused by ribose-5-phosphate isomerase deficiency [ 36 ].…”

Section: Discussionsupporting

confidence: 94%

Ribitol alters multiple metabolic pathways of central carbon metabolism with enhanced glycolysis: A metabolomics and transcriptomics profiling of breast cancer

et al. 2022

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Breast cancer is heterogenous in development and cell population with prognoses being highly dependent on numerous factors from driving mutations, biomarker expression and variation in extracellular environment, all affecting response to therapies. Recently, much attention has been given to the role of metabolic alteration in cancers, expanding from the Warburg effect to highlight unique patterns in different cancer cell populations for improving diagnostic and therapeutic approaches. We recently reported on modulation of mannosylation of α-dystroglycan with the metabolite ribitol in breast cancer lines. Here we investigate the effects of pentose sugars ribitol, ribose, and xylitol media supplementation in breast cancer cells by metabolomics and differential gene expression profiling. This combined approach revealed distinctive patterns of alterations in metabolic pathways by ribitol, contrasted with the closely related pentose ribose and pentitol xylitol. Significantly, ribitol supplementation enhances utilization of glucose by glycolysis, whereas ribose improves oxidative phosphorylation and fatty acid synthesis. Ribitol supplementation also increased levels of reduced glutathione (associated with a decrease in oxidative phosphorylation, gluconeogenesis), where ribose supplementation elevated levels of oxidized glutathione (GSSG) indicating an increase in oxidative stress. Treatment with ribitol also enhanced nucleotide biosynthesis. The apparent TCA cycle dysregulation, with distinctive pattern in response to the individual pentitol and pentose, such as ribitol increasing succinate and fumarate while decreasing citrate, demonstrate the adaptive capability of cancer cells to nutritional environment. This metabolic reprogramming presents new avenues for developing targeted therapies to cancers with metabolites, especially in combination with other drug treatments.

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Section: Discussionsupporting

confidence: 94%

Ribitol alters multiple metabolic pathways of central carbon metabolism with enhanced glycolysis: A metabolomics and transcriptomics profiling of breast cancer

et al. 2022

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“…Nevertheless, it was observed that ribitol facilitated a rise in the glutathione peroxidase, catalase, and superoxide dismutase activity. This effect is likely a result of an augmented generation of the superoxide radical [55].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Anti-Diabetic, Anti-Inflammatory, Antioxidant Activities and Toxicological Study of Optimized Psychotria malayana Jack Leaves Extract

Syed Mohamad,

Khatib,

So’ad

et al. 2023

Pharmaceuticals

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Psychotria malayana Jack (Family: Rubiaceae, local name: Salung) is a traditional herb used to treat diabetes. A previous study by our research group demonstrated that P. malayana methanolic and water extract exhibits significant potential as an effective agent for managing diabetes. Further research has been performed on the extraction optimization of this plant to enhance its inhibitory activity against α-glucosidase, a key enzyme associated with diabetes, and to reduce its toxicity. The objectives of this study are to evaluate the anti-diabetic, anti-inflammatory, and antioxidant properties of the optimized P. malayana leaf extract (OE), to evaluate its toxicity using a zebrafish embryo/larvae model, and to analyze its metabolites. The anti-diabetic effects were assessed by investigating α-glucosidase inhibition (AGI), while the inflammation inhibitory activity was performed using the soybean lipoxygenase inhibitory (SLOXI) test. The assessment of antioxidant activity was performed utilizing FRAP and DPPH assays. The toxicology study was conducted using the zebrafish embryo/larvae (Danio rerio) model. The metabolites present in the extracts were analyzed using GC-MS and LC-MS. OE demonstrated significant AGI and SLOXI activities, represented as 2.02 and 4.92 µg/mL for IC50 values, respectively. It exhibited potent antioxidant activities as determined by IC50 values of 13.08 µg/mL (using the DPPH assay) and 95.44 mmol TE/mg DW (using the FRAP assay), and also demonstrated an LC50 value of 224.29 µg/mL, which surpasses its therapeutic index of 111.03. OE exhibited a higher therapeutic index compared to that of the methanol extract (13.84) stated in the previous state of the art. This suggests that OE exhibits a lower level of toxicity, making it safer for use, and has the potential to be highly effective in its anti-diabetic activity. Liquid chromatography–mass spectrometry (LC-MS) and gas chromatography–mass spectrometry (GC-MS) demonstrated the presence of several constituents in this extract. Among them, several compounds, such as propanoic acid, succinic acid, D-tagatose, myo-inositol, isorhamnetin, moracin M-3′-O-β-D-glucopyranoside, procyanidin B3, and leucopelargonidin, have been reported as possessing anti-diabetic and antioxidant activities. This finding offers great potential for future research in diabetes treatment.

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“…The latter is based on the decreased striatal levels of mainly ribitol and pyroglutamic acid. Ribitol has been shown to increase oxidative stress/ROS production [ 37 ] and can be used to indicate cellular oxidative stress levels. Furthermore, pyroglutamic acid is an intermediate in glutathione metabolism, produced when glutathione is broken down (i.e., oxidized by ROS).…”

Section: Discussionmentioning

confidence: 99%

Untargeted Metabolomics Reveals the Potential Antidepressant Activity of a Novel Adenosine Receptor Antagonist

2022

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Depression is the most common mental illness, affecting approximately 4.4% of the global population. Despite many available treatments, some patients exhibit treatment-resistant depression. Thus, the need to develop new and alternative treatments cannot be overstated. Adenosine receptor antagonists have emerged as a promising new class of antidepressants. The current study investigates a novel dual A1/A2A adenosine receptor antagonist, namely 2-(3,4-dihydroxybenzylidene)-4-methoxy-2,3-dihydro-1H-inden-1-one (1a), for antidepressant capabilities by determining its metabolic profiles and comparing them to those of two reference compounds (imipramine and KW-6002). The metabolic profiles were obtained by treating male Sprague-Dawley rats with 1a and the reference compounds and subjecting them to the forced swim test. Serum and brain material was consequently collected from the animals following euthanasia, after which the metabolites were extracted and analyzed through untargeted metabolomics using both 1H-NMR and GC-TOFMS. The current study provides insight into compound 1a’s metabolic profile. The metabolic profile of 1a was similar to those of the reference compounds. They potentially exhibit their antidepressive capabilities via downstream effects on amino acid and lipid metabolism.

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Polyols accumulated in ribose‐5‐phosphate isomerase deficiency increase mitochondrial superoxide production and improve antioxidant defenses in rats' prefrontal cortex

Cited by 10 publications

References 28 publications

Ribitol alters multiple metabolic pathways of central carbon metabolism with enhanced glycolysis: A metabolomics and transcriptomics profiling of breast cancer

Ribitol alters multiple metabolic pathways of central carbon metabolism with enhanced glycolysis: A metabolomics and transcriptomics profiling of breast cancer

In Vitro Anti-Diabetic, Anti-Inflammatory, Antioxidant Activities and Toxicological Study of Optimized Psychotria malayana Jack Leaves Extract

Untargeted Metabolomics Reveals the Potential Antidepressant Activity of a Novel Adenosine Receptor Antagonist

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