Ascorbic deficient, animals

As indicated in Figure 2, when minces of tumor obtained from normal and ascorbic acid-deficient animals were incubated with C14-pro-line, much more radioactivity was incorporated into the collagen of the normal tissue. When the specific radioactivities of the isolated imino acids were examined (Table HI), several conclusions were possible. In the experiments with granuloma from normal animals and C14-proline, the values for hydroxyproline were not far from those of proline. With the scorbutic granulomas, the specific activity of the isolated proline was not greatly reduced, compared to that obtained from the normal granuloma. In contrast, the specific activity of the hydroxyproline isolated from the deficient tissues was markedly reduced. Similar results were obtained in the studies with tritiated proline. Thus, the specific activity of the proline isolated from the deficient granuloma was only moderately reduced, whereas the specific activity of the hydroxyproline was extremely low. This observation may be explained in terms of a dual-pathway mechanism of proline incorporation, considered below. 

Groups of normal and vitamin C deficient guinea pigs (21 d) were given 50 mg of ascorbic acid in their drinking water for 3, 6, and 10 a. Enzyme activity measured as fimol of product formedjh1100 mg of liver microsomal protein at 27° C. Key activity in normal animals, cross-hatched bar activity in vitamin C deficient animals, open bar vitamin C deficient animals given supplements of ascorbic acid for days indicated, solid bar. 

The data indicate that zinc-induced metallothionein binds mercury in the renal cortex and shifts the distribution of mercury from its site of toxicity at the epithelial cells of the proximal tubules. Thus, the renal content of mercury is increased, yet less is available to cause toxicity. In contrast, the renal toxicity of mercuric chloride is exacerbated in zinc-deficient animals (Fukino et al. 1992). In the zinc-deficient state, less mercury accumulates in the kidneys, but the toxicity is greater. The mechanism of the protection appears to involve more than simply a redistribution of renal mercury, because in the absence of mercury exposure, zinc deficiency increases renal oxidative stress (increased lipid peroxidation, decreased reduced ascorbate). When mercury exposure occurs, the oxidative stress is compounded (increased lipid peroxidation and decreased glutathione and glutathione peroxidase). Thus, zinc appears to affect the biochemical protective mechanisms in the kidneys as well. 

Terroine (1954) has examined the effect of ascorbic acid on biotin deficiency in rats. She used lower levels than in her later experiments on thiamine and riboflavin deficiencies. She found that 0.1-0.5% ascorbic acid only slightly improved growth and appetite but considerably reduced the incidence of signs of biotin deficiency. Thus, in 92 days, all the deficient animals had developed alopecia, but only 30% of those receiving ascorbic acid. Similarly, 90% of the deficient group had spectacle eyes, but none... 

The accumulation of pyruvic acid and a-ketoglutar-ate in vitamin C deficiency may be explained by the reduced concentration of CoA in ascorbic acid-deficient animals. The coenzyme is involved in the decarboxylation of both metabolites, but again, it has been suggested that the effect of ascorbic acid is secondary. The increased levels of pyruvic and lactic acids in blood could be caused by the insulin deficiency that develops in scorbutic animals. This conclusion finds support in the observation that fructose administration normalizes pyruvic and lactic acid levels. Whether the increased levels of a-ketoglutarate in scorbutic animals could result from decreased use in protein hydroxyla-tion remains to be seen. 

There have been several papers published which suggest that the synthesis of ascorbic acid is impaired in vitamin-deficient animals, with the conclusion that the action of this or that vitamin is necessary at one stage in the synthetic process. It is appropriate to review briefly here the evidence on which such conclusions are based. 

The evidence would therefore suggest that the lowered ascorbic acid content of tissues of vitamin A-deficient animals is due to inanition associated with the deficiency rather than to any specific effect of vitamin A on the synthesis of ascorbic acid. 

To some extent the vitamin E requirement may be lessened by the presence in the diet of synthetic antioxidants and by selenium. Much evidence supports a relationship between the nutritional need for selenium and that for vitamin E. Lack of either causes muscular dystrophy in many animals as well as severe edema (exudative diathesis) in chicks. Since vitamin E-deficient rats have a low selenide (Se2 ) content, it has been suggested that vitamin E protects reduced selenium from oxidation.) Vitamin C (ascorbic acid), in turn, protects vitamin E. 

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