Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036474 (scurvy)
 685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Guinea pigs were fed during 5 weeks with three different levels of vitamin C in the diet: 33 (marginal deficiency), 660, or 13,200 mg of vitamin C per kg of diet. The group fed 660 mg of vitamin C/kg of diet showed strongly reduced levels of protein carbonyls (46% decrease), malondialdehyde (HPLC; 72% decrease), and in vitro production of TBARS (both stimulated with ascorbate-Fe2+ and with NADPH-ADP-Fe2+; 68% and 71% decrease), increased glutathione reductase activity, and increased vitamin C content (48 times higher) in the liver in relation to the group fed 33 mg/kg. The treatment with 660 mg of vitamin C/kg did not decrease any of the antioxidant defenses studied: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, GSH, vitamin E, or uric acid. Further supplementation with 13,200 mg vitamin C/kg also reduced protein and lipid peroxidation, but decreased hepatic glutathione reductase and uric acid and resulted in a lower body weight of the animals. Both low (33 mg/kg) and very high (13,200 mg/kg) levels of vitamin C decreased body weight, glutathione reductase, and unsaturation of fatty acids in membrane lipids. The results show that a diet supplying an amount of vitamin C 40 times higher than the minimum daily requirement to avoid scurvy increases the global antioxidant capacity and is of protective value against endogenous lipid and protein oxidation in the liver under normal nonstressful conditions.
 ...
PMID:Dietary vitamin C decreases endogenous protein oxidative damage, malondialdehyde, and lipid peroxidation and maintains fatty acid unsaturation in the guinea pig liver. 795 71

Previous studies showed that administration of ascorbate to glutathione (GSH)-deficient newborn rats and guinea pigs prevented toxicity and mortality and led to increased tissue and mitochondrial GSH levels; ascorbate thus spares GSH. In the present work, we tried to answer the converse question: Does administration of GSH spare ascorbate? Because administered GSH is not well transported into most cells, we gave GSH monoethyl ester (which is readily transported and converted into GSH intracellularly) to guinea pigs fed an ascorbate-deficient diet. We found that treatment with GSH ester significantly delays appearance of the signs of scurvy and that this treatment spares ascorbate; thus, the decrease of tissue levels of ascorbate was delayed. The findings support the conclusions that (i) GSH is essential for the physiological function of ascorbate because it is required in vivo for reduction of dehydroascorbate and (ii) there is metabolic redundancy and overlap of the functions of these antioxidants. The sparing effect of GSH in scurvy may be mediated through an increase in the reduction of dehydroascorbate (which would otherwise be degraded) and to antioxidant effects of GSH that are also produced by ascorbate. Other studies indicate that GSH deficiency in adult mice stimulates ascorbate synthesis in liver. During this work we found that administration of GSH itself is highly toxic to ascorbate-deficient guinea pigs when given in divided i.p. doses totaling 3.75 mmol/kg daily.
 ...
PMID:Glutathione ester delays the onset of scurvy in ascorbate-deficient guinea pigs. 841 36

Previous studies indicate that benzanthrone, an anthraquinone dye intermediate, caused significant depletion of ascorbic acid (AsA). In this investigation the effect of benzanthrone on the status of different forms of AsA and other bio-antioxidants such as glutathione (GSH) was studied. Oral administration of benzanthrone (50, 125 or 250 mg/kg body weight) resulted in a significant increase of urinary AsA levels with a concomitant decrease in the urinary dehydroascorbic acid (DHA) content in both rats and guinea-pigs. Benzanthrone caused a dose-dependent decrease in hepatic, adrenal and serum AsA levels with a subsequent increase in DHA and diketogulonic acid (DKA) levels in both rats and guinea-pigs. Following benzanthrone treatment, rats showed an increase in the scorbutic index (to 1.01-1.21) of the liver, adrenal glands and serum compared to controls (0.12-0.24). The scorbutic indices of liver, adrenal glands and serum were also substantially increased (to 3.61-11.20) in benzanthrone-treated guinea-pigs compared to controls (0.16-0.38). Single oral administration of benzanthrone to guinea-pigs caused a dose-dependent depletion of GSH in liver (15-51%), adrenal glands (27-64%) and serum (32-86%). Furthermore, the depletion of GSH by benzanthrone in rats was of a lesser degree. This suggests that continued exposure of guinea-pigs to benzanthrone may lead to scurvy-type changes in this animal species but not to the same extent in rats, since the latter has the enzymatic capacity to synthesise AsA. Therefore, it can be hypothesised that benzanthrone per se, or its metabolites, interact with reduced GSH thereby causing its depletion. Furthermore, in order to replenish the depleted GSH levels, AsA might be oxidized to DHA and hence the decrease in AsA with the simultaneous increase in DHA was observed.
 ...
PMID:Role of biological antioxidants in benzanthrone toxicity. 1148 20

Although the coordination of various antioxidants is important for the protection of organisms from oxidative stress, dynamic aspects of the interaction of endogenous antioxidants in vivo remain to be elucidated. We studied the metabolic coordination of two naturally occurring water-soluble antioxidants, ascorbic acid (AA) and reduced glutathione (GSH), in liver, kidney and plasma of control and scurvy-prone osteogenic disorder Shionogi (ODS) rats that hereditarily lack the ability to synthesize AA. When supplemented with AA, its levels in liver and kidney of ODS rats increased to similar levels of those in control rats. Hepato-renal levels of glutathione were similar with the two animal groups except for the slight increase in its hepatic levels in AA-supplemented ODS rats. Administration of L-buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, rapidly decreased the hepato-renal levels of glutathione in a biphasic manner, a rapid phase followed by a slower phase. Kinetic analysis revealed that glutathione turnover was enhanced significantly in liver mitochondria and renal cytosol of ODS rats. Administration of BSO significantly increased AA levels in the liver and kidney of control rats but decreased them in AA-supplemented ODS rats. Kinetic analysis revealed that AA is synthesized by control rat liver by some BSO-enhanced mechanism and the de novo synthesized AA is transferred to the kidney. Such a coordination of the metabolism of GSH and AA in liver and kidney is suppressed in AA-deficient ODS rats. These and other results suggest that the metabolism of AA and GSH forms a compensatory network by which oxidative stress can be decreased.
 ...
PMID:Metabolic cooperation of ascorbic acid and glutathione in normal and vitamin C-deficient ODS rats. 1175 33