Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003969 (vitamin C deficiency)
 625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of long-term chronic ascorbic acid deficiency and excessive ascorbic acid consumption on bile acid metabolism and biliary lipid composition were studied in guinea pigs. Male, weanling guinea pigs were fed a cereal-based scorbutigenic diet for 19 or 21 weeks. Ascorbic acid was administered either orally at 0.15 (group A) or 2.0 (group B) mg/100 g body weight, or it was mixed in the diet at levels of 500 (group C), 16-22 (group D), or 20,000 mg/kg (group E). Chronic ascorbic acid deficiency (groups A and D) caused depression of hepatic cytochrome P-450 levels and elevation of plasma cholesterol. Excessive ascorbate consumption did not alter these parameters relative to control levels. In contrast to results obtained in guinea pigs fed low or high amounts of ascorbate for 7-9 weeks, prolonged consumption of inadequate or excessive ascorbate resulted in little or no change in bile acid metabolism and biliary lipid composition except that bile acid pool size was increased 12% as a result of excessive ascorbate ingestion. Results of the present study suggest that there may be important differences in the guinea pig's metabolic response to ascorbic acid deficiency and ascorbic acid excess, depending on the length of the experimental period.
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PMID:Long-term effects of inadequate and excessive dietary ascorbate on bile acid metabolism in the guinea pig. 674 20

Studies were carried out to characterize the response of hepatic mixed function oxidase (MFO) activity to chronic ascorbic acid deficiency and excessive ascorbic acid intake in the guinea pig. When guinea pigs were fed excessive ascorbic acid, there was a small increase in hepatic cytochrome P-450 which was unaccompanied by any alteration in drug-metabolizing enzyme activity. Similarly, induction of MFO activity by phenobarbital was not modified by excessive ascorbic acid administration. Chronic ascorbic acid deficiency resulted in depressed metabolism of aniline, aminopyrine, ethoxycoumarin and benzphetamine, but not of ethylmorphine, in comparison with animals fed diets containing control and/or excessive amounts of ascorbic acid. In contrast to the metabolism of all drugs studied, the 7 alpha-hydroxylation of cholesterol was depressed by both inadequate and excessive vitamin C intake, demonstrating the unique sensitivity of cholesterol 7 alpha-hydroxylase to dietary ascorbate.
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PMID:Dietary ascorbic acid and hepatic mixed function oxidase activity in the guinea pig. 683 Jun 22

Hepatic heme oxygenase activity was significantly altered in vitamin C-deficient guinea pigs. It was increased two-fold after 14 days and was decreased by 20% after 21 days of deprivation of the vitamin (always in comparison with the control value). The apparent Km of the enzyme was also altered in the course of ascorbic acid deficiency. The data of hepatic heme oxygenase activity correspond to previous results on the metabolism of hepatic cytochrome P-450 in different stages of ascorbic acid deprivation. Splenic heme oxygenase activity decreased progressively arriving at 50% of the control value after 21 days of vitamin C omission, its apparent Km remained unaltered.
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PMID:Activity of microsomal heme oxygenase in liver and spleen of ascorbic acid-deficient guinea pigs. 689 16

Reports of the beneficial effects of large doses of ascorbic acid have stressed its water solubility and non-toxic properties. In this study male guinea pigs, dosed with 150 mg twice daily, ascorbic acid, demonstrated no differences in effect on liver weight, body weight or hepatic total protein when compared with controls. The activities of NADPH-dependent cytochrome c reductase, N-demethylase (Type I) and O-de-ethylase enzymes (Type II) remained unaffected, but the activity of the Type I hydroxylating enzyme, biphenyl-4-hydroxylase, and the amounts of cytochromes P-450 and b5 were significantly reduced. Total microsomal haem proteins were reduced and mirrored the effects in cytochromes P-450 and b5. The rate-limiting enzyme in haem synthesis, delta-amino-laevulinic acid synthetase, rose in the ascorbic acid group and this was associated with a fall in activity of the haem degrading enzyme, microsomal haem oxygenase. Thus, large amounts of ascorbic acid have similar effects to those found in scorbutic animals and appear to interfere with the construction of the cytochrome P-450 molecule.
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PMID:Effect of large doses of ascorbic acid on the mixed function oxidase system in guinea pig liver. 709 49

Although interaction of vitamin C, copper and iron have been studied in several species, little is known about these interactions in species which require the vitamin in the diet. Young male Hartley guinea pigs were fed a basal diet, or a basal diet and supplemented daily with vitamin C, p.o. Pharmacologic doses (25 mg per 100 g BW per day) of vitamin C resulted in two-to-three-fold decreases in liver copper, when compared with those receiving normal (0.5 mg per 100 g BW per day) intakes. Under conditions of vitamin C deficiency, serum copper and ceruloplasmin were elevated along with liver copper. Serum and hepatic iron levels, hepatic microsomal cytochrome P-450 and cytochrome b5, and blood heme parameters all appeared to be directly related to vitamin C intake, i.e. the iron and heme parameters increased as the vitamin dose increased. These data are consistent with the hypothesis that interaction between vitamin C, copper and iron influence normal heme formation through the oxidation/reduction of iron and/or by regulating iron absorption and availability at the gut level.
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PMID:Effect of vitamin C on copper and iron metabolism in the guinea pig. 742 59

Effect of unsaturated and saturated fats on cholesterol metabolism was studied in ascorbate sufficient and deficient guineapigs. Experimental animals were made chronic ascorbic acid deficient by allowing oral intake of 0.5 mg ascorbic acid/day/animal. Elevation in serum and liver cholesterol and triglyceride along with depression in cholesterol oxidation and 7 alpha-hydroxylation in liver was observed in unsaturated fat fed guineapigs with ascorbate deficiency. Liver microsomal cytochrome P-450 level was found to be low in ascorbate deficient animals. Polyunsaturated fat intake could not lower the serum cholesterol level in ascorbate deficiency. Today polyunsaturated fat in the diet is encouraged all over the world for its hypocholesterolemic effect. This study indicates that polyunsaturated fat intake with ascorbic acid deficiency may produce hypercholesterolemia.
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PMID:Interrelationship of dietary lipids and ascorbic acid with hepatic enzymes of cholesterol metabolic pathway. 927 32

The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. First, male ODS rats were fed a diet containing sufficient ascorbic acid (control) or a diet without ascorbic acid (deficient) for 18 days, with or without the intraperitoneal injection of phenobarbital. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Next, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver.
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PMID:Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats. 2503 35


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