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


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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    • "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.
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