Influence of <scp>D</scp>‐arabitol and ribitol on neuronal network activity

Klusmann, A.; Fleischer, Wiebke; Waldhaus, Anne; Siebler, Mario; Mayatepek, Ertan

doi:10.1007/s10545-005-0073-2

Cited by 5 publications

(3 citation statements)

References 9 publications

(8 reference statements)

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“…In agreement with our findings, Klusmann et al (2005) evaluated the neurotoxicity of d ‐arabitol and ribitol, using a neurochip model representing cortical neurons of rats. The exposure of up to 10 mM of polyols did not alter the spontaneous network activity of neurons, indicating the absence or only a secondary effect of polyols on brain dysfunction.…”

Section: Discussionsupporting

confidence: 80%

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

Stone

Kudo

August

et al. 2014

Intl J of Devlp Neuroscience

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The ribose-5-phosphate isomerase deficiency is an inherited condition, which results in cerebral d-arabitol and ribitol accumulation. Patients present leukoencephalopathy, mental retardation, and psychomotor impairment. Considering that the pathophysiology of this disorder is still unclear, and literature are sparse and contradictory, reporting pro and antioxidant activities of polyols, the main objective of this study was to investigate some parameters of oxidative homeostasis of prefrontal cortex of rats incubated with d-arabitol and ribitol. We found evidences that ribitol promoted an increase in antioxidant enzymes activity (superoxide dismutase, catalase, and glutathione peroxidase), probably secondary to enhanced production of superoxide radical, measured by flow cytometry. Oxidation of proteins and lipids was not induced by polyols. Our data allow us to conclude that, at least in our methodological conditions, arabitol and ribitol probably have a secondary effect on the pathophysiology of ribose-5-phosphate isomerase deficiency.

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Section: Discussionsupporting

confidence: 80%

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

Stone

Kudo

August

et al. 2014

Intl J of Devlp Neuroscience

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“…Pathological accumulation of polyols might play a role in secondary neuronal damage associated with metabolic diseases, 68,69 even though a direct neurotoxic effect could not be demonstrated. 70…”

Section: Metabolic Correlates Of Neuronal Injury As Biomarkers and Clues To Understanding The Neurodegenerative Processmentioning

confidence: 99%

The Mouse Brain Metabolome

Jaeger

Glaab

Michelucci

et al. 2015

The American Journal of Pathology

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Neurodegeneration is a multistep process characterized by a multitude of molecular entities and their interactions. Systems analyses, or omics approaches, have become an important tool in characterizing this process. Although RNA and protein profiling made their entry into this field a couple of decades ago, metabolite profiling is a more recent addition. The metabolome represents a large part or all metabolites in a tissue, and gives a snapshot of its physiology. By using gas chromatography coupled to mass spectrometry, we analyzed the metabolic profile of brain regions of the mouse, and found that each region is characterized by its own metabolic signature. We then analyzed the metabolic profile of the mouse brain after excitotoxic injury, a mechanism of neurodegeneration implicated in numerous neurological diseases. More important, we validated our findings by measuring, histologically and molecularly, actual neurodegeneration and glial response. We found that a specific global metabolic signature, best revealed by machine learning algorithms, rather than individual metabolites, was the most robust correlate of neuronal injury and the accompanying gliosis, and this signature could serve as a global biomarker for neurodegeneration. We also observed that brain lesioning induced several metabolites with neuroprotective properties. Our results deepen the understanding of metabolic changes accompanying neurodegeneration in disease models, and could help rapidly evaluate these changes in preclinical drug studies.

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“…Christensson et al [25] reported the diagnosis of D-arabinitol/L-arabinitol ratios in urine in neutropenic children with cancer for the invasive candidiasis. In addition, Klusmann et al [26] reported that highly elevated concentrations of the C5 polyols, such as arabitol, were found in body fluids in the disorder of ribose-5-phosphate isomerase deficiency. In our study, arabitol was found to be increased in the serum of ovarian cancer patients and the ovarian benign tumor patients, compared to the healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Expanded metabolomics approach to profiling endogenous carbohydrates in the serum of ovarian cancer patients

Cheng

Zhu

et al. 2015

J of Separation Science

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We applied hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry to the quantitative analysis of serum from 58 women, including ovarian cancer patients, ovarian benign tumor patients, and healthy controls. All of these ovarian cancer and ovarian benign tumor patients have elevated cancer antigen 125, which makes them clinically difficult to differentiate the malignant from the benign. All of the 16 endogenous carbohydrates were quantitatively detected in the human sera, of which, eight endogenous carbohydrates were significantly different (P-value < 0.05) between the ovarian cancer and healthy control. According to the receiver operating characteristic curve analysis, arabitol was the most potentially specific biomarker for discriminating ovarian cancer from healthy control, having an area under the curve of 0.911. A panel of metabolite markers composed of maltose, maltotriose, raffinose, and mannitol was selected, which was able to discriminate the ovarian cancer from the benign ovarian tumor counterparts, with an area under concentration-time curve value of 0.832. Endogenous carbohydrates in the expanded metabolomics approach after the global metabolic profiling are characterized and are potential biomarkers for the early diagnosis of ovarian cancer.

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Influence of D‐arabitol and ribitol on neuronal network activity

Cited by 5 publications

References 9 publications

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

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

The Mouse Brain Metabolome

Expanded metabolomics approach to profiling endogenous carbohydrates in the serum of ovarian cancer patients

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