Changes in collagen cross-link ratios in bone and urine of guinea pigs fed graded dietary vitamin C: a functional index of vitamin C status

Mild-to-moderate vitamin C depletion in weanling guinea-pigs affects pyridinoline:deoxypyridinoline (collagen cross-link) ratios in femur shaft and urine, attributed to impairment of hydroxylation of collagen lysine. We investigated: (1) whether the picture at two time points is compatible with progressive accumulation of abnormal collagen; (2) whether any changes are seen in skin, where little deoxypyridinoline occurs; (3) whether total food restriction has similar effects. Male weanling Dunkin–Hartley guinea-pigs were fed diets containing either 0·5 (vitamin C-restricted) or 160·0–320·0 (vitamin C-adequate) mg vitamin /. Two groups receiving the vitamin C-adequate diet received it ad libitum. Two other groups received the vitamin C-adequate diet in a restricted amount, limited to that which permitted nearly the same growth rate as in the vitamin C-restricted groups. Animals were fed for 4 or 8 weeks; urine was collected, and vitamin C and collagen indices were measured. In the femur shaft, the hydroxyproline content per unit weight was unaffected by vitamin C restriction or by total food restriction. Deoxypyridinoline was increased and the pyridinoline:deoxypyridinoline ratio was decreased in vitamin C-restricted groups, but not in food-restricted groups. Changes in the value of the ratio were greater after 8 than after 4 weeks. Urine indices mirrored bone indices. In skin, the main effect of vitamin C restriction was to reduce hydroxyproline. Here, the cross-link ratios changed less markedly than in bone, and there was less deoxypyridinoline. We conclude that the picture at two time points is compatible with a progressive accumulation of pyridinoline-enriched collagen in vitamin C-deprived animals, that the picture in skin differs from that of bone and urine, and that cross-link changes are not produced by total food restriction.

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Effects of age and dietary vitamin C on the contents of ascorbic acid and acid-soluble thiol in lens and aqueous humour of guinea-pigs

Experimental Eye Research ◽

10.1016/s0014-4835(88)80045-9 ◽

1988 ◽

Vol 46 (6) ◽

pp. 937-945 ◽

Cited By ~ 16

Author(s):

Christopher J. Bates ◽

Terence D. Cowen

Keyword(s):

Ascorbic Acid ◽

Vitamin C ◽

Guinea Pigs ◽

Aqueous Humour ◽

Dietary Vitamin

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Vitatmin C and bone markers: investigations in a Gambian population

Proceedings of The Nutrition Society ◽

10.1079/pns2003247 ◽

2003 ◽

Vol 62 (2) ◽

pp. 429-436 ◽

Cited By ~ 2

Author(s):

Karen Munday

Keyword(s):

Vitamin C ◽

Antioxidant Properties ◽

Population Group ◽

Bone Collagen ◽

Dietary Vitamin ◽

Cross Link ◽

Formation Pathway ◽

Collagen Formation ◽

Beneficial Effects ◽

Tissue Vitamin

Vitamin C is an essential micronutrient. Absence from the diet will result in the deficiency disease scurvy, typically characterised by weakening of collagenous structures. High intakes of vitamin C have been associated with decreased incidence or severity of a number of diseases, including cancer and cardiovascular disease. These beneficial effects may be attributed to its antioxidant properties, although the exact mechanisms of action remain elusive. It is also unclear what intake levels are required for optimal health benefits. The task of defining optimal intakes is hindered by the lack of a reliable functional marker of tissue vitamin C status in man. Many different pathways have been investigated, but none of them have measurable outcome variables relating directly to scorbutic changes. The bone-collagen formation pathway has the potential to provide a functional index of tissue vitamin C adequacy. Vitamin C acts as a cofactor for the enzyme lysyl hydroxylase, which is required for the hydroxylation of lysine residues in procollagen chains. Pyridinoline is a mature collagen cross-link formed from three hydroxylysine residues, deoxypyridinoline is formed from two hydroxylysine and one lysine residue. Guinea-pig studies have shown an alteration in the pyridinium cross-link ratios in response to graded vitamin C intakes ‘Tsuchiya & Bates, 1998’. In order to investigate whether these changes can be seen in a human population group, a study was carried out in rural Gambia, where there is a marked seasonal variation in dietary vitamin C. The present review discusses the rationale behind the study and presents some preliminary results.

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Vitamin C and copper interactions in guinea-pigs and a study of collagen cross-links

British Journal Of Nutrition ◽

10.1079/bjn19970032 ◽

1997 ◽

Vol 77 (2) ◽

pp. 315-325 ◽

Cited By ~ 18

Author(s):

H Tsuchiya ◽

C. J Bates†

Keyword(s):

Ascorbic Acid ◽

Superoxide Dismutase ◽

Guinea Pigs ◽

Significant Interaction ◽

Cross Link ◽

Functional Index ◽

Body Weights ◽

Blood Haemoglobin ◽

Metabolic Interactions ◽

Cross Links

The purpose of this study was, first to explore metabolic interactions between Cu and ascorbic acid in guinea-pigs, particularly with respect to any possible disadvantages of high ascorbatein the presence of low Cu intakes, and second, to test the hypothesis that variations in ascorbate and/or Cu status might inhence collagen cross-linking, either by inducing a change in thecross-links: hydroxyproline ratio, or by inducing a change in the pyridinoline: deoxypyridinoline cross-linls ratio. Four matched groups, each of eight male weanliig Dunkin-Hartley guinea-pigs, were maintained on purified diets containing either no added Cu, or 150 mg Cu/kg diet, and either 0·1 g or 30 g ascorbic acid/kg diet. They were then killed 8 weeks later, and the following indices were measured body and organ weights; blood haemoglobin; adrenal ascorbate concentrations; Cu concentrations in plasma, liver and femur; superoxide dismutase (EC 1.15.1.1) activity in whole blood and liver; hydroxyproline, pyridinoline and deoxypyridinoline in femur and in urine. The principal observations were: Cu intake significantly affected blood and tissue Cu concentrations and superoxide dismutase activity; and ascorbic acid intake significantlyaffected adrenal ascorbate levels and the deoxypyridinoline: pyridinoline cross-links ratio, especially in bone (femur). There was evidence of a significant interaction between ascorbateand Cu with respect to adrenal and plasma Cu concentrations, blood superoxide dismutase activityand body weights. We conclude that interactions between ascorbate and Cu at the functional level were present but modest, and that a new and potentially powerful functional index of ascorbate status may exist within the deoxypyridinoline: pyridinoliie collagen cross-link ratio.

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Effects of a Dietary Oxidized Fat on Cholesterol in Plasma and Lipoproteins and the Susceptibility of Low-density Lipoproteins to Lipid Peroxidation in Guinea Pigs Fed Diets with Different Concentrations of Vitamins E and C

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.74.1.11 ◽

2004 ◽

Vol 74 (1) ◽

pp. 11-20 ◽

Cited By ~ 12

Author(s):

Eder ◽

Keller ◽

Brandsch

Keyword(s):

Lipid Peroxidation ◽

Vitamin C ◽

Guinea Pigs ◽

Low Density Lipoproteins ◽

Alpha Tocopherol ◽

Dietary Vitamin ◽

Low Density ◽

Vitamins E And C ◽

Fat Diets ◽

Oxidized Fat

To investigate the effect of a dietary oxidized fat on the concentrations of cholesterol in liver, plasma, and lipoproteins and the susceptibility of low-density lipoproteins (LDL) to lipid peroxidation, and to explore the effects of vitamins E and C, male guinea pigs were divided into five groups. Four groups were fed diets with an oxidized fat supplemented with 35 or 175 mg alpha-tocopherol equivalents/kg and 300 or 1000 mg of vitamin C/kg for 29 days. One group, used as a control, was fed the same basal diet with fresh fat with 35 mg alpha-tocopherol equivalents/kg and 300 mg of vitamin C/kg. Guinea pigs fed the oxidized-fat diets, irrespective of dietary vitamin E and C concentrations, had significantly lower concentrations of total cholesterol in the liver and a lower concentration of cholesterol in LDL than the control animals fed the fresh fat. According to the lag time before onset of lipid peroxidation, LDL of guinea pigs fed the oxidized-fat diet with 35 mg alpha-tocopherol equivalents and 300 mg vitamin C/kg were significantly more susceptible to copper-induced lipid peroxidation than those of guinea pigs fed the fresh fat diet. Within the groups fed the oxidized fat diets, increasing the dietary vitamin E concentration from 35 to 175 mg/kg significantly (p < 0.05) and increasing the dietary vitamin C concentration from 300 to 1000 mg/kg in tendency (p < 0.10) reduced the susceptibility of LDL to oxidation. LDL of guinea pigs fed the oxidized fat diets with 175 mg alpha-tocopherol equivalents/kg were even more resistant to oxidation than LDL of guinea pigs fed the fresh diet. In conclusion, the study shows that dietary oxidized fat influences the cholesterol metabolism and the susceptibility of LDL to lipid peroxidation; the latter can be modified by dietary vitamins E and C.

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