The effect of chronic hypovitaminosis C on the metabolism of cholesterol and atherogenesis in guinea pigs

Ginter, E; J, Babala; Cervén, J

doi:10.1016/s0368-1319(69)80037-2

Cited by 42 publications

(11 citation statements)

References 14 publications

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“…However, the guinea pig is in a remarkable way different. It has been reported that atherosclerotic deposits in the arteries of the guinea pig were formed on an ascorbatedeficient diet without additional cholesterol (33). We have verified that these deposits are not formed by guinea pigs given higher doses of ascorbate but are formed by the animals on an ascorbate-deficient diet without the administration of large amounts of cholesterol (unpublished experiments).…”

Section: The Guinea Pig As An Animal Model For Atherosclerosissupporting

confidence: 70%

Hypothesis: lipoprotein(a) is a surrogate for ascorbate.

Rath

Pauling

1990

Proc. Natl. Acad. Sci. U.S.A.

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The concept that lipoprotein (a) [Lp(a)] is a surrogate for ascorbate is suggested by the fact that this lipoprotein is found generally in the blood of primates and the guinea pig, which have lost the ability to synthesize ascorbate, but only rarely in the blood of other animals. Properties of Lp(a) that are shared with ascorbate, in accordance with this hypothesis, are the acceleration of wopnd healing and other cell-repair mechanisms, the strengthening of the extracellular matrix (e.g., in blood vessels), and the prevention of lipid peroxidation. High plasma Lp(a) is associated with coronary heart disease and other forms ofatherosclerosis in humans, and the incidence of cardiovascular disease is decreased by elevated ascorbate. Similar observations have been made in cancer and diabetes. We have formulated the hypothesis that Lp(a) is a surrogate for ascorbate in humans and other species and have marshaled the evidence bearing on this hypothesis.Lipoproteins consist of particles, each of which is a globule of lipid molecules surrounded by an apoprotein shell. Lipoprotein(a) [Lp(a)] was discovered by Blumberg et al. (1) and by Berg (2). It shares with low density lipoprotein (LDL) its lipid and apoprotein composition-mainly apoprotein B-100 (apo B), consisting of a polypeptide chain of 4536 amino acid residues. The unique feature of Lp(a) is an additional glycoprotein, designated apoprotein(a) [apo(a)], which is linked to apo B by disulfide groups. The cDNA sequence of apo(a) (3) shows a striking homology to plasminogen, with multiple repeats of kringle 4, one kringle 5, and a protease domain. The isoforms of apo(a) vary in the range of 300 to 800 kDa and differ mainly in their genetically determined number of kringle 4 structures (3); apo(a) has no plasmin-like protease activity (4), but a serine protease activity has been demonstrated recently (5). Like plasminogen, Lp(a) has been shown to bind to lysine-Sepharose, immobilized fibrin and fibrinogen (6), and the plasminogen receptor on endothelial cells (7)(8)(9). This binding is inhibited by E-aminocaproic acid, certain other amines, and plasminogen.

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Section: The Guinea Pig As An Animal Model For Atherosclerosissupporting

confidence: 70%

Hypothesis: lipoprotein(a) is a surrogate for ascorbate.

Rath

Pauling

1990

Proc. Natl. Acad. Sci. U.S.A.

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“…Guinea pigs fed a cholesterol diet consume a larger amount of AA, resulting in a decrease in AA level of organs (14,19). In our experiments II and III, several symptoms of chronic AA deficiency such as body weight loss, roughness of hair, keratinization in limbs, necrosis of the ear, changes in relative organ weight were observed in guinea pigs fed diet II with 0.5 or 1.0% cholesterol.…”

Section: Discussionmentioning

confidence: 51%

Fundamental Studies on Physiological and Pharmacological Actions of L-Ascorbate 2-Sulfate. Vi. Effects of L-Ascorbate 2-Sulfate on Lipid Metabolism in Guinea Pigs

Hayashi¹,

Yamada²,

Kunitomo³

et al. 1978

Japanese Journal of Pharmacology

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Abstract-Effectsof L-ascorbate 2-sulfate (AAS) on lipid metabolism were studied in guinea pigs maintained on diet I with sufficient L-ascorbic acid (AA) supplement or on diet II without AA supplement. AAS (300 mg/kg) inhibited an increase in serum and liver levels of lipids to a greater degree than AA (175 mg/kg), a reference compound, in hyperlipidemic guinea pigs induced by cholesterol feeding with diets I or II. AAS also induced a decrease in serum and liver levels of lipids in guinea pigs which had been previously maintained for 6 weeks on diet II containing 1.0 % cholesterol. AA admin istration significantly increased AA level in various organs of animals maintained on both the diets containing cholesterol. It also rectified the AA level lowered by previous maintenance on diet lI containing cholesterol.AAS showed a slight AA replacing effect on the AA level. Both AA and AAS exerted preventive and curative effects on several symptoms due to chronic AA deficiency. L-Ascorbate2-sulfate (AAS) recently found in animals (1-4), has drawn attention to the effects on lipid metabolism (5).We reported in previous papers that AAS exerts lipid lowering effects in experimental hyperlipidemia with mice, rats and rabbits, and prevents development of atherosclerosis (6, 7). In an attempt to dissociate the effect of AAS from that of L-ascorbic acid (AA), the present study of AAS on lipid metabolism has been carried out in guinea pigs which do not to biosynthesize AA in vivo. MATERIALS AND METHODS Materials:The compounds examined for hypolipidemic effects were sodium L ascorbate 2-sulfate-3 H2O and sodium L-ascorbate.Preventive effects of AAS and AA on hyperlipidemia (Experiment I and II): The experi mental design is shown in Table 1. Male guinea pigs of Hartley strain, weighing 250 to 300 g were divided into 8 groups of 4 or 5. In experiment I, preventive effects of AAS and AA on hyperlipidemia induced by cholesterol feeding were studied with diet I (RC-4 of Oriental Yeast Co., Tokyo) which was supplemented with 50 nag of AA per 100 g. In experiment 11, these effects were examined with diet II (AA-unsupplemented diet of Fuji Mill Co., Shizuoka) which contained 9 mg of AA per 100 g.

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“…It is difficult to elicit vitamin C deficiency in animal models. In view of the conflicting observations based on the acutely scorbutic animal model chosen by most of the workers, Ginter et al [83] designed a model of chronic latent vitamin C deficiency in guinea pigs. This model in contrast to others, enabled the effect of AA deficiency on lipid metabolism and atherosclerosis to be followed in long term experiments.…”

Section: Vitamin C and Atherosclerosismentioning

confidence: 99%

“…This model in contrast to others, enabled the effect of AA deficiency on lipid metabolism and atherosclerosis to be followed in long term experiments. In protracted hypovitaminosis C lasting for 10 weeks, there was a considerable accumulation of cholesterol in liver and also increased concentration in serum [83][84][85].…”

Section: Vitamin C and Atherosclerosismentioning

confidence: 99%

“…It was also reported that the deficiency of vitamin C leads to enhanced accumulation of cholesterol in thoracic aorta along with pathomorphological changes in blood vessels [83,86,87]. Various human trials have also indicated vitamin C induced reduction in blood lipid levels in normal and hypercholesterolemic subjects [88,89].…”

Section: Vitamin C and Atherosclerosismentioning

confidence: 99%

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Vitamin C in Disease Prevention and Cure: An Overview

et al. 2013

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The recognition of vitamin C is associated with a history of an unrelenting search for the cause of the ancient haemorrhagic disease scurvy. Isolated in 1928, vitamin C is essential for the development and maintenance of connective tissues. It plays an important role in bone formation, wound healing and the maintenance of healthy gums. Vitamin C plays an important role in a number of metabolic functions including the activation of the B vitamin, folic acid, the conversion of cholesterol to bile acids and the conversion of the amino acid, tryptophan, to the neurotransmitter, serotonin. It is an antioxidant that protects body from free radical damage. It is used as therapeutic agent in many diseases and disorders. Vitamin C protects the immune system, reduces the severity of allergic reactions and helps to fight off infections. However the significance and beneficial effect of vitamin C in respect to human disease such as cancer, atherosclerosis, diabetes, neurodegenerative disease and metal toxicity however remains equivocal. Thus further continuous uninterrupted efforts may open new vistas to understand its significance in disease management.

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The effect of chronic hypovitaminosis C on the metabolism of cholesterol and atherogenesis in guinea pigs

Cited by 42 publications

References 14 publications

Hypothesis: lipoprotein(a) is a surrogate for ascorbate.

Hypothesis: lipoprotein(a) is a surrogate for ascorbate.

Fundamental Studies on Physiological and Pharmacological Actions of L-Ascorbate 2-Sulfate. Vi. Effects of L-Ascorbate 2-Sulfate on Lipid Metabolism in Guinea Pigs

Vitamin C in Disease Prevention and Cure: An Overview

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