Excretion Of Ascorbic Acid Research Articles

Effect of supplementing methionine and threonine to a non-protein diet on the induction of enzymes by polychlorinated biphenyls in rats.

The N-sparing action of methionine and threonine in rats fed with a non-protein diet seems to indicate that methionine and threonine are the endogenously most-limiting amino acids. The effect of a dietary supplementation of methionine and threonine to a non-protein diet on enzyme induction by polychlorinated biphenyls (PCB) was investigated. Liver microsomal drug-metabolizing enzymes were further induced by the methionine and threonine supplement to the non-protein diet in PCB-receiving rats. Although feeding with PCB did not increase the urinary ascorbic acid excretion in rats of the non-protein diet group, the supplementation of methionine and threonine to the non-protein diet markedly increased this excretion. From these observations, dietary methionine and threonine might promote the synthesis of drug-metabolizing enzymes and the enzymes related to ascorbic acid biosynthesis in PCB-receiving rats.

Abnormalities of ascorbic acid metabolism and diabetic control: differences between diabetic patients and diabetic rats

Ascorbic acid is required in the synthesis of collagen and is also an important anti-oxidant. In a previous study, plasma ascorbic acid concentration was found to be decreased in diabetic patients but there was no relationship with blood glucose level. In the current study of diabetic patients, both plasma ascorbic acid and its urinary excretion correlated inversely with glycosylated hemoglobin level. Plasma ascorbic acid was also lower in diabetic rats but urinary ascorbic acid was elevated. The divergent trend in urinary ascorbic acid excretion observed in diabetic patients and diabetic rats may be due to difference in the ability of these two species to synthesize ascorbic acid. Difference in renal reabsorption of ascorbic acid may also be a relevant factor. The lower plasma and urinary ascorbic acid levels in diabetic patients with more severe hyperglycaemia indicates that this group of patients is particularly at risk of developing deficiency of this vitamin. As ascorbic acid has many important functions in the body, it may be necessary to supplement this vitamin in patients with chronically poorly controlled diabetes.

Ascorbic Acid Metabolism and Polyol Pathway in Diabetes

It has been reported previously that the plasma concentration of ascorbic acid (AA) is reduced in streptozocin-induced diabetic rats and can be normalized by treatment with the aldose reductase inhibitor tolrestat. This study was designed to investigate further the relationship between the polyol pathway and AA metabolism in diabetic rats. Disturbance of AA metabolism was demonstrable after 1 wk of diabetes. Dietary myo-inositol supplementation was effective in normalizing plasma AA levels, as was treatment with tolrestat. In untreated diabetes, despite low plasma AA concentration, there was increased urinary excretion of AA that was reversed by treatment with either tolrestat or myo-inositol. In contrast, AA supplementation normalized plasma AA concentrations while further increasing urinary AA excretion. The abnormality of AA metabolism was less severe in galactose-fed rats, which had normal plasma AA levels and only minor increases in urinary AA excretion. These studies demonstrated a disturbance in the regulation of plasma and urinary AA concentration in experimental diabetes and confirmed the relationship of AA with the polyol pathway. Because AA has many important biological functions, abnormalities of AA metabolism could be important in the pathogenesis of some diabetic complications. The interaction of the polyol and AA pathways suggests that this could be another site of action for aldose reductase inhibitors.

Effects of dietary ethanol on ascorbic acid and lipid metabolism, and liver drug-metabolizing enzymes in rats.

Effects of dietary ethanol on ascorbic acid and lipid metabolism, and liver drug-metabolizing enzymes in rats fed a semi-purified diet containing a powdered ethanol preparation (30 cal% in the diet) were studied. Administration of ethanol increased urinary ascorbic acid excretion (p less than 0.001) and ascorbic acid level in the liver (p less than 0.001) and the spleen (p less than 0.01). The activity of hepatic aniline hydroxylase was increased (p less than 0.05) by ethanol feeding but that of aminopyrine N-demethylase was not. Increases of serum total and high-density-lipoprotein (HDL) cholesterol level, commonly observed by the administration of xenobiotics, were not observed. These results showed ethanol possessed rather similar properties to xenobiotics such as polychlorinated biphenyls (PCB) or 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane (DDT) in some metabolic changes. In this study, no accumulation of lipid in the liver was observed.

Urinary Ascorbic Acid Levels Following the Withdrawal of Large Doses of Ascorbic Acid in Guinea Pigs

Male guinea pigs received sodium ascorbate solution [equivalent to 1 g ascorbic acid/(kg body weight.d)] by intraperitoneal injection for 4 wk. During the ascorbic acid treatment period, plasma and urinary ascorbic acid levels rose markedly. Three weeks after the ascorbic acid treatment was withdrawn, mean urinary ascorbic acid levels were significantly lower than their corresponding basal levels. At both 2 and 5 wk after withdrawal of ascorbic acid treatment, mean plasma ascorbic acid levels were below normal. The results indicate that these animals had experienced a transient withdrawal effect after administration of large doses of ascorbic acid that lasted about 1 wk. This, in turn, indicates that the rate of ascorbic acid turnover was probably increased during treatment, and this effect persisted even after the ascorbic acid was withdrawn. Examination of data from each individual experimental animal revealed that the pattern of urinary ascorbic acid excretion after the withdrawal of large doses of ascorbic acid varied from animal to animal. Among the twelve experimental guinea pigs, seven had abnormally low urinary ascorbic acid levels 2-4 wk after the withdrawal of the large doses of ascorbic acid.

Effect of polychlorinated biphenyls on lipids and ascorbic acid metabolism in streptozotocin-induced diabetic rats.

Metabolic changes in lipids, ascorbic acid, and hepatic microsomal cytochrome P-450 by feeding polychlorinated biphenyls (PCB) were investigated in streptozotocin-induced diabetic rats. Streptozotocin (STZ, 60 mg/kg body weight) was injected in Wistar male rats intraperitoneally. Diabetic and non-diabetic rats were fed ad libitum a 20% casein-based control diet or a PCB-containing diet (200 mg/kg diet) for 9 days. Body weight decreased significantly in STZ-induced diabetic rats with or without PCB (groups PD and D, respectively). In rats of group D, urinary ascorbic acid excretion was 15 times higher than that in non-diabetic rats fed a control diet (group C). Dietary PCB caused 30-fold higher urinary ascorbic acid excretion in non-diabetic rats (group P) than that in group C. In group PD, urinary ascorbic acid was nearly 60 times higher than that in group C. Ascorbic acid in liver and kidney was significantly lower in group D than in group C, and it was significantly lower in group PD than in group P. Liver microsomal cytochrome P-450 and b5 were both increased by dietary PCB in group P. Addition increase in these enzymes was observed in diabetic rats by PCB. Serum total cholesterol was 1.8 times higher in group P than in group C. Further increase in serum total cholesterol was observed in group PD. These data suggest that metabolic changes in lipids and ascorbic acid induced by the dietary xenobiotic were magnified in STZ-induced diabetic rats.

Long-Term Effects of Dietary Polychlorinated Biphenyl and High Level of Vitamin E on Ascorbic Acid and Lipid Metabolism in Rats

Long-term feeding of purified diets containing (per kg diet) 100 mg of polychlorinated biphenyl (PCB) and 1000 mg of vitamin E (RRR-α-tocopheryl acetate) to male Wistar rats was carried out. Rats fed a diet containing PCB rapidly became hypercholesterolemic and maintained high cholesterol levels throughout the 240 d of the experiment. Rats fed a high dietary level of vitamin E plus PCB had higher serum cholesterol and lower liver cholesterol than rats fed a lower level of vitamin E plus PCB. In rats fed PCB, urinary excretion of ascorbic acid was higher than in rats not fed PCB. Urinary ascorbic acid was lower in rats fed high levels of vitamin E plus PCB than in those fed the normal levels of vitamin E plus PCB. Rats fed PCB had lower liver vitamin A storage and higher vitamin A in kidney than rats not fed PCB. This implies that a redistribution of vitamin A occurred in rats fed PCB. Histological observations revealed that central halves of the hepatic lobules of rats fed PCB showed distinct changes consisting of hypertrophy of hepatocytes in the perivenous region and accumulation of vacuoles (lipid droplets) in the cells in the remaining affected portion. Administration of a high dose of vitamin E could not ameliorate this lesion while the treatment depressed effectively the lipid peroxidation. This suggests that the lipid peroxidation was not responsible for the hepatic damage induced by PCB.

ALCOHOL ENHANCES VITAMIN C EXCRETION IN THE URINE

Urinary ascorbic acid excretion was measured on four consecutive days in 9 normal male volunteers for 4 hr before and after drinking nothing (control), 0.58 g alcohol/kg body wt as whisky or lager or water (11./70 kg body wt). The normal reduction in ascorbic acid excretion under control conditions was abolished by drinking water. Alcohol in either form produced a 47% increase in urinary ascorbic acid excretion. A similar ascorbiuresis in chronic alcoholics would be an additional factor in the causation of vitamin C deficiency in these patients.

Ascorbic acid status of australian antarctic expeditiones

It is not certain that all personnel active in polar regions receive adequate dietary ascorbic acid. Leucocyte ascorbic acid concentrations were measured during the year of an Australian Antarctic expedition with half the personnel taking a supplement of 1000 mg of the vitamin/day. The results, together with a urinary ascorbic acid excretion study and medical monitoring, indicate that the Australian rations supply adequate dietary ascorbic acid which comes largely from canned fruit juice. Supplemental ascorbic acid is advised for field rations. One man suffered a possible complication of ascorbic acid megadosage.

Evidence of rebound effect with ascorbic acid

The urinary excretion pattern of ascorbic acid in two subjects who had been taking a large amount of ascorbic acid (10 g per day) and later reverted to a small intake (125 mg per day) is described. The ascorbic acid concentration in the 24-hour urine samples was measured over a 40-day collection of this period. The mean urinary ascorbic acid excretion during the loading period of the two subjects was about 2 g per day. Upon termination of the high intake of ascorbic acid, urinary ascorbic acid excretion dropped to presupplementation levels within 6 days. Urinary ascorbic acid of the two subjects continued to decrease to below basal level, and remained at abnormally low levels for 10 and 12 days respectively. We hypothesize that the high intake of ascorbic acid has induced the formation of increased amounts of enzymes that help convert the ascorbic acid into other substances and that these substances are valuable. Some possible physiological actions of these ascorbic acid metabolites are discussed.

Decrease in Urinary Excretion of Ascorbic Acid and Histamine in Rats after Repeated Immobilization Stress

Feeding rats an ascorbic acid-free diet led to a gradual decrease in urinary excretion of ascorbic acid, which reached an equilibrium of approximately 350 µg/day/100 g of body weight after 18 days. The urinary level of histamine also decreased steadily on this diet. Consecutive 4-hour daily immobilization stress resulted in a marked reduction in the urinary output of ascorbic acid in rats fed this diet: from 357 ± 6 µg/day per 100 g of body weight (mean ± SEM, n = 6) to 224 ± 13 (-37%, P < 0.01) after 6 days. The amount of ascorbic acid in the serum, liver and adrenal glands fell significantly. There was a marked reduction in urinary excretion of histamine under immobilization stress. Both urinary ascorbic acid and histamine tended to return toward their original values after cessation of the stress regimen. The implications of these observations are discussed in relation to a possible natural defense mechanism of animals against stressful stimuli.

Effect of oral contraceptive agents on ascorbic acid metabolism in the rhesus monkey

Ascorbic acid (AA) metabolism was studied in six sexually mature female rhesus monkeys with normal menstrual cycles before and during oral contraceptive administration. The animals were fed a commercial monkey stock diet (15% protein) containing no AA and given a 100 mg AA tablet daily throughout the study. After an initial adaptation period and a control period (total 8 months), combined-type oral contraceptive agents (OCAs) (50 micrograms mestranol and 1 mg norethindrone for 21 days each month) were administered to each monkey for 4 months. Serum copper and ceruloplasmin were significantly elevated during OCA treatment. There were no significant changes in plasma or leukocyte AA values during OCA use; however, urinary AA excretion decreased significantly. During the last month of the control period and the 3rd month of OCA treatment, 50 muCi of 1-14C-L-ascorbic acid were injected intravenously into each monkey. Urinary excretion of radioactivity, measured for 1 month, indicated a significantly faster AA turnover rate during the period of OCA use. These results suggest that women using OCAs may have an increased dietary requirement for AA.

Effects of Some Xenobiotics on Ascorbic Acid Metabolism in Rats

The administration of xenobiotics, PCB, DDT, or aminopyrine to rats causes a marked increase in urinary excretion of ascorbic acid and in various tissue levels of ascorbic acid. When rats were fed diet containing 200 ppm PCB or 500 ppm DDT (14 days), the incorporations from d-(U-14C) glucose into ascorbic acid in liver were significantly increased. The dietary addition of 200 ppm PCB, 500 ppm DDT, 2,000 ppm pentobarbital or 3,000 ppm chloretone caused a significant increase in the activity of hepatic UDPglucose dehydrogenase, but did not affect the activity of hepatic l-gulonolactone oxidase. Good correlation between the liver level of ascorbic acid and the activity of hepatic UDPglucose dehydrogenase was observed. Subsequently, in rats fed the basal diet (30% casein diet) or the diet containing 200 ppm PCB, the specific activities of ascorbic acid in urine and in various tissues were measured 6 hours, 12 hours and 24 hours after the oral administration of l-(1-14C)ascorbic acid. Dietary PCB accelerated the disappearances of radioactivities in ascorbic acid in urine and various tissues, that is, shortened the half lives of radioactivities in ascorbic acid. It is likely that the administration of xenobiotics, such as PCB or DDT, to rats increases the biosynthesis of ascorbic acid and accelerates concomitantly the turnover of ascorbic acid in body.PCB DDT xenobiotics ascrobic acid

The excretion of ascorbic acid and hippuric acid in the urine of rats with liver injury.

The excretion of ascorbic acid and hippuric acid in the urine as liver function tests has no marked advantages when compared with other tests (activities of serum enzymes glutamate dehydrogenase and L-alanine: 2-oxoglutarate aminotransferase, hexobarbital sleeping time).

Tyrosyluria in marasmus.

1. Plasma tyrosine and urinary p-hydroxyphenyl lactic acid (PHPLA) and p-hydroxyphenyl acetic acid (PHPAA) were studied in thirty patients with marasmus and twenty normal controls in the same age group. 2. In the control group conventional tyrosyluria was not observed but 30% of the group excreted high levels of PHPAA. In the group with marasmus, plasma tyrosine and urinary PHPLA and PHPAA values were signigificantly higher than the control values. However only 13.3% of the patients were considered to have conventional tyrosyluria and 52.3% were found to excrete high levels of PHPAA. 3. Administration of ascorbic acid resulted in a reduction of PHPLA excretion while it had no effect on PHPAA excretion. 4. It was inferred that (a) tyrosyluria in marasmus is due to the reduced activity of the hepatic enzyme 4-hydroxyphenyl pyruvate: oxygen oxidoreductase (hydroxylating, decarboxylating) (PHPAA-oxidase; EC 1.13.11.27) due to the deficiency of ascorbic acid and (b) high excretion of PHPAA is related to age and nutrition of the child and is unaffected by the administration of ascorbic acid. 5. It was further inferred that urinary excretion of PHPLA is a reliable index of tyrosyluria.

Metabolism of ascorbic acid (vitamin C) in subjects infected with common cold viruses

The influence of experimentally induced rhinovirus infection on the excretion of ascorbic acid (AA) and two of its possible metabolites, diketogulonic acid (DKG) and oxalic acid was determined in human volunteers receiving a controlled daily intake of AA. There was a significant fall in the excretion of both AA and DKG in the infected subjects but no change in the oxalic acid excretion. A simple absorption test provided no evidence of any impairment of gastrointestinal absorption of AA during infection. Possible mechanisms of this infection-induced change in AA metabolism are discussed.

Urinary ascorbic acid excretion in the human as affected by dietary fiber and zinc

The objective of the project was to study the effect of dietary pectin, cellulose, hemicellulose, and zinc on human urinary excretion of ascorbic acid. The project consisted of two 33-day controlled feeding studies involving a total of 19 adult men and women of normal health. Within each study all subjects received all experimental treatments. In study A during the four 7-day experimental periods the ground peanut based diets were varied as follows: no supplement, 14.2 g of hemicellulose supplement, 14.2 g of cellulose supplement, or 14.2 g of pectin supplement per subject per day. Mean urinary excretion of ascorbic acid by subjects while receiving these supplements were 26.10, 32.27, 26.27, or 20.60 mg/day, respectively. In study B during the four 7-day randomly arranged experimental periods, the following alterations were made to the basal diet: supplement of 14.2 g of pectin plus 1.3 g of zinc, 14.2 g of pectin plus 9.3 g of zinc, 4.2 g pectin plus 1.3 g of zinc, and 4.2 g of pectin plus 9.3 g of zinc. Mean urinary ascorbic acid excretion of subjects while receiving these diets were as follows: 20.61, 23.18, 28.07, 18.99. Hemicellulose supplement enhanced urinary excretion of ascorbic acid while pectin and zinc resulted in decreased urinary excretion of this vitamin. Increased urinary excretion of ascorbic acid at constant intake levels is thought usually to be indicative of enhanced absorption or of decreased need.

The effect of carcinogenic chemicals on ascorbic acid metabolism

Carcinogenic chemicals, their analogues and other ascorbic acid influencing drugs are reviewed with respect to their ability to alter the metabolism and excretion of ascorbic acid. The influence of hormones and studies with scorbutic animals are also included. The various mechanisms proposed for explaining the increase in synthesis and excretion of ascorbic acid induced by carcinogens are summarized.

Megadosage of ascorbic acid in an Antarctic expedition.

1. No difference in health was observed between men on megadosage of ascorbic acid and controls during the year of an Antarctic expedition. 2. All men appeared to have a satisfactory intake of ascorbic acid throughout the year. 3. There was a statistically significant decrease in excretion of ascorbic acid by men on megadosage over the year, and by the controls. 4. The decline in excretion by the control group may be explained by dietary change, but the decline in those on megadosage may be due to altered handling of ascorbic acid by the body. 5. No complications due to megadosage of ascorbic acid were observed.

Supplementation and excretion of ascorbic acid in healthy women

Supplementation and excretion of ascorbic acid in healthy women