Biochemistry of uridine in plasma

Yamamoto, Tetsuya; Koyama, Hideki; Kurajoh, Masafumi; Shoji, Takuhito; Tsutsumi, Zenta; Moriwaki, Yuji

doi:10.1016/j.cca.2011.06.006

Cited by 85 publications

(89 citation statements)

References 108 publications

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“…This correlates well with the liver being the major organ responsible for homeostatic control of uridine plasma and tissue concentrations (Yamamoto et al. 2011). …”

Section: Discussionmentioning

confidence: 99%

ADME studies of [5‐³H]‐2′‐O‐methyluridine nucleoside in mice: a building block in siRNA therapeutics

Lozac'h

Christensen

Faller

et al. 2016

Pharmacology Res & Perspec

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The chemical modification 2′‐O‐methyl of nucleosides is often used to increase siRNA stability towards nuclease activities. However, the metabolic fate of modified nucleosides remains unclear. Therefore, the aim of this study was to determine the mass balance, pharmacokinetic, and absorption, distribution, metabolism, and excretion (ADME)‐properties of tritium‐labeled 2′‐O‐methyluridine, following a single intravenous dose to male CD‐1 mice. The single intravenous administration of [5‐3H]‐2′‐O‐methyluridine was well tolerated in mice. Radioactivity was rapidly and widely distributed throughout the body and remained detectable in all tissues investigated throughout the observation period of 48 h. After an initial rapid decline, blood concentrations of total radiolabeled components declined at a much slower rate. [3H]‐2′‐O‐Methyluridine represented a minor component of the radioactivity in plasma (5.89% of [3H]‐AUC 0‐48 h). Three [3H]‐2′‐O‐methyluridine metabolites namely uridine (M1), cytidine (M2), and uracil (M3) were the major circulating components representing 32.8%, 8.11%, and 23.6% of radioactivity area under the curve, respectively. The highest concentrations of total radiolabeled components and exposures were observed in kidney, spleen, pineal body, and lymph nodes. The mass balance, which is the sum of external recovery of radioactivity in excreta and remaining radioactivity in carcass and cage wash, was complete. Renal excretion accounted for about 52.7% of the dose with direct renal excretion of the parent in combination with metabolism to the endogenous compounds cytidine, uracil, cytosine, and cytidine.

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“…This correlates well with the liver being the major organ responsible for homeostatic control of uridine plasma and tissue concentrations (Yamamoto et al. 2011). …”

Section: Discussionmentioning

confidence: 99%

ADME studies of [5‐³H]‐2′‐O‐methyluridine nucleoside in mice: a building block in siRNA therapeutics

Lozac'h

Christensen

Faller

et al. 2016

Pharmacology Res & Perspec

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“…For Nucleosides, guanosine has many trophic effects in the central nervous system, including the stimulation of neurotrophic factor synthesis and release by astrocytes, which protect neurons against excitotoxic death (DiIorio et al, 2004). Uridine, is an essential component of RNA synthesis and plays an important role in the synthesis of glycogen (Yamamoto et al, 2011). In humans, uridine is administered to reduce the adverse effects of cancer chemotherapy, such as bone marrow and gastrointestinal toxicity (Yamamoto et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Physiological Active Substance Changes of Soybean Curd Residue Fermented by <i>Preussia aemulans</i> and its Bioactivity

Li¹,

Meng²,

Shi³

et al. 2016

American Journal of Biochemistry and Biotechnology

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A new species of fungus Preussia aemulans isolated from the Cordyceps sinensis fruiting body was cultured by soybean curd residue using solid-state fermentation method. The content of polysaccharide, amino acid, protein, phenolics and nucleoside were massively improved under the optimum conditions, including 10% adding dosage of glucose, 3% adding dosage of beef extract, 15 days of fermentation time. The crude Polysaccharide (CPS) fraction indicated significant immunomodulatory activity on macrophage RAW 264.7 cells and the Ethyl Acetate Extract (EAE) fraction revealed the moderate anti-proliferation ability on human colon cancer cell DLD-1 at high concentration. Both of CPS and EAE showed excellent antioxidant activities properties. The results were demonstrated that the fermented Soybean Curd Residue (SCR) could be utilized as nontoxic, safe and functional food, food additive and feed.

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“…It is a pyrimidine nucleoside required for synthesis of RNA, glycogen, bio-membranes and hence, essential for cellular growth, function and metabolism [185]. In humans, uridine is present in plasma, cerebrospinal fluid and seminal fluid and its concentration varies from 3-8 µM in the body [185,186].…”

Section: Uridinementioning

confidence: 99%

“…Sugar cane, tomatoes, broccoli and beer are rich in uridine. However, due to low bioavailability and rapid metabolism of uridine, the body depends upon pyrimidine salvage for uridine retrieval [186].…”

Section: Uridinementioning

confidence: 99%

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Systemic and local regulation of experimental arthritis by IFN-α, dendritic cells and uridine

Narendra¹

2017

Linköping University Medical Dissertations

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In this thesis, we have studied the immunological processes of joint inflammation that may be targets for future treatment of patients with arthritis. We focus on the immune-modulating properties of interferon-α (IFN-α) and uridine in experimental arthritis. The nucleoside uridine, which is regarded a safe treatment has anti-inflammatory properties notably by inhibiting tumor necrosis factor (TNF) release. Because the inflamed synovium in rheumatoid arthritis (RA) is characterised by pathogenic TNF-production, uridine could potentially be away to ameliorate arthritis. Systemic administration of uridine had no effect on antigeninduced arthritis (AIA), which is a T-cell dependent model where animals are immunized twice (sensitization) with bovine serum albumin (mBSA), before local triggering of arthritis by intra-articular antigen (mBSA) re-challenge. In contrast, intra-articular administration of uridine clearly down modulated development of AIA in a dose dependent manner and inhibited the expression of synovial adhesion molecules, influx of inflammatory leukocytes and synovial expression of TNF and interleukin 6, but did not affect systemic levels of proinflammatory cytokines or antigen-specific T-cell responses. Local administration of uridine may thus be a viable therapeutic option for treatment of arthritis in the future. Viral double-stranded deoxyribonucleic acid (dsRNA), a common nucleic acid found in most viruses, can be found in the joints of RA patients and local deposition of such viral dsRNA induces arthritis by activating IFN-α. Here we show that arthritis induced by dsRNA can be mediated by IFN-producing dendritic cells in the joint and this may thus explain why viral infections are sometimes associated with arthritis. Earlier, to study the effect of dsRNA and IFN-α in an arthritis model, that like RA, is dependent on adaptive immunity, dsRNA and IFN-α were administered individually during the development of AIA. Both molecules clearly protected against AIA in a type I IFN receptor-dependent manner but were only effective if administered in the sensitization phase of AIA. Here we show that the anti-inflammatory effect of IFN-α is critically dependent on signalling via transforming growth factor β (TGF-β) and the enzymatic activity of indoleamine 2,3 dioxygenase 1 (IDO). The IDO enzyme is produced by plasmacytoid DC and this cell type was critically required both during antigen sensitization and in the arthritis phase of AIA for the protective effect of IFN-α against AIA. In contrast, TGF-β and the enzymatic activity of IDO were only required during sensitization, which indicate that they are involved in initial steps of tolerogenic antigen sensitization. In this scenario, IFN- α first activates the enzymatic activity of IDO in pDC, which converts Tryptophan to Kynurenine, which thereafter activates TGF-β. Common for IDO-expressing pDC, Kyn and TGF-β is their ability to induce development of regulatory T cells (Tregs). We found that Tregs were crucial for IFN-α-mediated protection against AIA, but onl...

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Biochemistry of uridine in plasma

Cited by 85 publications

References 108 publications

ADME studies of [5‐³H]‐2′‐O‐methyluridine nucleoside in mice: a building block in siRNA therapeutics

ADME studies of [5‐³H]‐2′‐O‐methyluridine nucleoside in mice: a building block in siRNA therapeutics

Physiological Active Substance Changes of Soybean Curd Residue Fermented by <i>Preussia aemulans</i> and its Bioactivity

Systemic and local regulation of experimental arthritis by IFN-α, dendritic cells and uridine

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Biochemistry of uridine in plasma

Cited by 85 publications

References 108 publications

ADME studies of [5‐3H]‐2′‐O‐methyluridine nucleoside in mice: a building block in siRNA therapeutics

ADME studies of [5‐3H]‐2′‐O‐methyluridine nucleoside in mice: a building block in siRNA therapeutics

Physiological Active Substance Changes of Soybean Curd Residue Fermented by <i>Preussia aemulans</i> and its Bioactivity

Systemic and local regulation of experimental arthritis by IFN-α, dendritic cells and uridine

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Product

Resources

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ADME studies of [5‐³H]‐2′‐O‐methyluridine nucleoside in mice: a building block in siRNA therapeutics

ADME studies of [5‐³H]‐2′‐O‐methyluridine nucleoside in mice: a building block in siRNA therapeutics