The Analysis of Vitamin C Concentration in Organs of Gulo-/- Mice Upon Vitamin C Withdrawal

Department of Anatomy, Medical Research Center, Seoul National University, Seoul 110-799, Korea.
Immune Network 02/2012; 12(1):18-26. DOI: 10.4110/in.2012.12.1.18
Source: PubMed

ABSTRACT Vitamin C is an essential nutrient for maintaining human life. Vitamin C insufficiency in the plasma is closely related with the development of scurvy. However, in vivo kinetics of vitamin C regarding its storage and consumption is still largely unknown.
We used Gulo(-/-) mice, which cannot synthesize vitamin C like human. Vitamin C level in plasma and organs from Gulo(-/-) mice was examined, and it compared with the level of wild-type mice during 5 weeks.
The significant weight loss of Gulo(-/-) mice was shown at 3 weeks after vitamin C withdrawal. However, there was no differences between wild-type and vitamin C-supplemented Gulo(-/-) mice (3.3 g/L in drinking water). The concentration of vitamin C in plasma and organs was significantly decreased at 1 week after vitamin C withdrawal. Vitamin C is preferentially deposited in adrenal gland, lymph node, lung, and brain. There were no significant changes in the numbers and CD4/CD8 ratio of splenocytes in Gulo(-/-) mice with vitamin C withdrawal for 4 weeks. And the architecture of spleen in Gulo(-/-) mice was disrupted at 5 weeks after vitamin C withdrawal.
The vitamin C level of Gulo(-/-) mice was considerably decreased from 1 week after vitamin C withdrawal. Vitamin C is preferentially stored in some organs such as brain, adrenal gland and lung.

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    • "Gulo −/− mice were made VitC deficient by reducing VitC supplementation (0.033 g/L) for 1 week, followed by complete removal of dietary VitC for additional 2 weeks. We and others have shown that this reduced supplementation significantly decreases the concentration of VitC in immune cells, plasma, and organs [27] [31] [32]. "
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    ABSTRACT: Introduction: Macrophage reprogramming is vital for resolution of acute inflammation. Parenteral vitamin C (VitC) attenuates proinflammatory states in murine and human sepsis. However information about the mechanism by which VitC regulates resolution of inflammation is limited. Methods: To examine whether physiological levels of VitC modulate resolution of inflammation, we used transgenic mice lacking L-gulono-γ-lactone oxidase. VitC sufficient/deficient mice were subjected to a thioglycollate-elicited peritonitis model of sterile inflammation. Some VitC deficient mice received daily parenteral VitC (200 mg/kg) for 3 or 5 days following thioglycollate infusion. Peritoneal macrophages harvested on day 3 or day 5 were examined for intracellular VitC levels, pro- and anti-inflammatory protein and lipid mediators, mitochondrial function, and response to lipopolysaccharide (LPS). The THP-1 cell line was used to determine the modulatory activities of VitC in activated human macrophages. Results: VitC deficiency significantly delayed resolution of inflammation and generated an exaggerated proinflammatory response to in vitro LPS stimulation. VitC sufficiency and in vivo VitC supplementation restored macrophage phenotype and function in VitC deficient mice. VitC loading of THP-1 macrophages attenuated LPS-induced proinflammatory responses. Conclusion: VitC sufficiency favorably modulates macrophage function. In vivo or in vitro VitC supplementation restores macrophage phenotype and function leading to timely resolution of inflammation.
    Mediators of Inflammation 09/2014; 2014:173403. DOI:10.1155/2014/173403 · 3.24 Impact Factor
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    • "However, there was no evident weight change in Gulo-/- mice after 3 weeks of ascorbic acid withdrawal. This result is in agreement with our previous report on time- and organ-specific changes in in vivo ascorbic acid concentration in Gulo-/- mice [16]. Interestingly, despite the absence of weight loss, there was a remarkable loss of trabecular bone volume near to the growth plate in Gulo-/- mice after 3 weeks of ascorbic acid withdrawal (Fig. 5). "
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    ABSTRACT: The L-gulono-γ-lactone oxidase gene (Gulo) encodes an essential enzyme in the synthesis of ascorbic acid from glucose. On the basis of previous findings of bone abnormalities in Gulo (-/-) mice under conditions of ascorbic acid insufficiency, we investigated the effect of ascorbic acid insufficiency on factors related to bone metabolism in Gulo (-/-) mice. Four groups of mice were raised for 4 weeks under differing conditions of ascorbic acid insufficiency, namely, wild type; ascorbic acid-sufficient Gulo (-/-) mice, 3-week ascorbic acid-insufficient Gulo (-/-) mice, and 4-week ascorbic acid-insufficient Gulo (-/-) mice. Four weeks of ascorbic acid insufficiency resulted in significant weight loss in Gulo (-/-) mice. Interestingly, average plasma osteocalcin levels were significantly decreased in Gulo (-/-) mice after 3 weeks of ascorbic acid insufficiency. In addition, the tibia weight in ascorbic acid-sufficient Gulo (-/-) mice was significantly higher than that in the other three groups. Moreover, significant decreases in trabecular bone volume near to the growth plate, as well as in trabecular bone attachment to the growth plate, were evident in 3- or 4-week ascorbic acid-insufficient Gulo (-/-). In summary, ascorbic acid insufficiency in Gulo (-/-) mice results in severe defects in normal bone formation, which are closely related to a decrease in plasma osteocalcin levels.
    Anatomy & cell biology 12/2013; 46(4):254-61. DOI:10.5115/acb.2013.46.4.254
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    ABSTRACT: Dietary antioxidants are essential nutrients that inhibit the oxidation of biologically important molecules and suppress the toxicity of reactive oxygen or nitrogen species. When the total antioxidant capacity is insufficient to quench these reactive species, oxidative damage occurs and contributes to the onset and progression of chronic diseases, such as neurodegenerative diseases, cardiovascular diseases, and cancer. However, epidemiological studies that examine the relationship between antioxidants and disease outcome can only identify correlative associations. Additionally, many antioxidants also have prooxidant effects. Thus, clinically relevant animal models of antioxidant function are essential for improving our understanding of the role of antioxidants in the pathogenesis of complex diseases as well as evaluating the therapeutic potential and risks of their supplementation. Recent progress in gene knockout mice and virus-based gene expression has potentiated these areas of study. Here, we review the current genetically modified animal models of dietary antioxidant function and their clinical relevance in chronic diseases. This review focuses on the 3 major antioxidants in the human body: vitamin C, vitamin E, and uric acid. We examine genetic models of vitamin C synthesis (guinea pig, Osteogenic Disorder Shionogi rat, Gulo(-/-) and SMP30(-/-) mouse mutants) and transport (Slc23a1(-/-) and Slc23a2(-/-) mouse mutants), vitamin E transport (Ttpa(-/-) mouse mutant), and uric acid synthesis (Uox(-/-) mouse mutant). The application of these models to current research goals is also discussed.
    Journal of Nutrition 11/2012; 143(1). DOI:10.3945/jn.112.168690 · 3.88 Impact Factor
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