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Biomedical subjects

J M Rivers

Publications and source records attributed to J M Rivers.

At least 19 recordsLinked to original sources
PubMed1990

Effect of increasing storage iron on ascorbic acid metabolism in the guinea pig.

Ascorbic acid (AA) metabolism was studied in control and iron-loaded guinea pigs. All animals were fed an AA-deficient diet and given a daily intraperitoneal (ip) dose of 10 mg sodium ascorbate. The control-diet formula contained 0.10 g Fe/kg diet; the experimental diet contained an additional 3.33 g Fe/kg diet as FeSO4. After 14 wk animals were injected (ip) with 9.25 x 10(3) Bq [1-14C]L-ascorbic acid. Blood was collected for 10 d and plasma specific activity of AA was determined. All animals were subsequently killed and selected tissues were analyzed for AA and iron concentrations. In spite of marked elevation of iron concentrations in plasma, spleen, and liver in experimental animals compared with controls, no differences in AA metabolism as determined by tissue AA concentrations and AA half-life, turnover rate, and body-pool size were evident. These results demonstrate that iron loading has no effect on the rate of AA catabolism in guinea pigs.

Animals↗
PubMed1989

Safety of high-level vitamin C ingestion.

Reports suggesting that gram doses of ascorbic acid are beneficial for the prevention and treatment of several disorders have led to widespread ingestion of vitamin C supplements. Possible adverse health effects of this practice have, therefore, received considerable scrutiny. Of major concern has been the influence of ingesting gram amounts of ascorbic acid on renal calcium oxalate stones, systemic conditioning, uricosuria, vitamin B12 destruction, mutagenicity, and iron overload. Despite contradictory reports, the consensus from an extensive literature is that these adverse health effects are not induced in healthy persons by ingesting large doses of ascorbic acid. Possible interactions of ascorbic acid with other nutrients and physiological processes may be of importance to human health and, therefore, merit further research. The ingestion of large doses of ascorbic acid is contraindicated in cases of renal insufficiency, chronic hemodialysis patients, unusual forms of iron overload, and oxalate stoneformers.

Ascorbic Acid↗
PubMed1987

Uptake and release of adrenal ascorbic acid in the guinea pig after injection of ACTH.

The effect of a single injection of ACTH (3 IU/100 g body weight) on the distribution of ascorbic acid (AA) and radiolabeled AA in 20 tissues was studied in adult male guinea pigs consuming 500 mg AA/kg diet. Saline- or ACTH-injected animals were simultaneously injected with [1-14C]AA, and killed at 0.5, 1, 2, 4 and 6 h after injection. There was no significant difference between treatments in the weight of any tissue over the 6-h experimental period. As anticipated, the concentration of AA in the adrenals of animals injected with ACTH was 33% of that of animals injected with saline at 4 h. Unexpectedly, the concentration of radiolabeled AA in the adrenals at 0.5 h after ACTH injection was 172% of that after saline injection. The concentration of radiolabeled AA in the adrenal of the saline-injected animals increased slowly over time to reach a level similar to that of ACTH-injected animals by 6 h. There was no effect of ACTH on the level of AA or uptake in any of the other tissues examined. These results demonstrate that a single dose of ACTH markedly influences the retention of AA in the adrenal gland without similarly altering retention of AA in other tissues. Furthermore, ACTH treatment causes both accelerated uptake and release of AA into the adrenals.

Adrenal Glands↗
PubMed1987

The effect of bilateral adrenalectomy on metabolism and tissue distribution of ascorbic acid in the rat.

Adult, male, Sprague-Dawley rats were injected with [1-14C] -ascorbic acid 11 days post bilateral adrenalectomy or sham-adrenalectomy, and immediately placed in metabolism chambers. Excreta (CO2 and urine) were collected for 48 hours. The animals were then sacrificed and 10 tissues were processed and assayed for total ascorbic acid (AA) and radioactivity. There was no significant difference in weight gain between groups post-operation. Adrenalectomized rats excreted significantly less radioactivity, resulting in a significantly longer estimated half-life of AA (173 +/- 7 h) than the sham-adrenalectomized controls (141 +/- 7 h). Weights of tissues were similar between groups. The concentration of AA was significantly higher (43%) in the heart and lower (17%) in the liver in adrenalectomized animals. This group of animals also had significantly higher levels of radioactivity in the heart (51%), kidney, and spleen (19%). The specific activity of AA (% dose/mg AA) was not different between groups for any tissue examined. These results demonstrate that adrenalectomy affects the degradation of AA and its concentration in selected tissues, with a profound effect on the heart.

Adrenalectomy↗
PubMed1984

Long-term effects of inadequate and excessive dietary ascorbate on bile acid metabolism in the guinea pig.

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.

Administration, Oral↗
PubMed1984

Comparison of isotope dilution and excretion methods for determining the half-life of ascorbic acid in the guinea pig.

The half-life of ascorbic acid (AA) in guinea pigs was investigated by the isotope dilution and excretion methods. The dilution method measures [1-14C]AA disappearance from the plasma, whereas the excretion method measures the elimination of [1-14C]AA and the metabolites from the body. Two groups of animals underwent both isotope studies in reverse order. Animals were conditioned to the experimental procedures and fed 2.5 mg AA/100 g body weight orally to maintain a daily intake of the vitamin independent of food consumption. The two isotope procedures imposed similar stress on the animals, as determined by plasma cortisol levels and body weight changes. The AA half-life calculations of the rapidly exchangeable pool by the isotope dilution method yielded values of 1.23 and 0.34 hours for the two groups, respectively. The half-life of the slowly exchangeable pool for the two groups was 60.2 and 65.8 hours, respectively. The half-life of AA in the rapidly exchangeable pool, as measured by the excretion studies, was 4.57-8.75 hours. For the slowly exchangeable pool, it was 146-149 hours. The longer half-life of both pools obtained with the excretion method indicates that the isotope is disappearing from the plasma more rapidly than it is being excreted. This suggests that a portion of the [1-14C]AA leaving the plasma is removed to a body pool that is not sampled by the isotope excretion method.

Animals↗
PubMed1984

Influence of dietary ascorbic acid on cholesterol 7 alpha-hydroxylase activity in the rat.

An experiment was carried out to determine whether dietary excess of ascorbic acid inhibits cholesterol 7 alpha-hydroxylase activity and elevates cholesterol levels in the rat, as previously observed in the guinea pig. Male, weanling Sprague-Dawley rats were fed a cereal-based diet supplemented with 0, 0.5, 10.0, or 20.0 g ascorbate/kg for 45 days. Ascorbate supplementation did not alter plasma ascorbate levels in the rat, but did increase hepatic ascorbate at the highest dietary intakes (10.0 and 20.0 g ascorbate/kg diet). Ascorbate supplementation had no effect upon plasma and liver cholesterol levels or cholesterol 7 alpha-hydroxylase activity. Under the experimental conditions employed, the rat appears resistant to ascorbate-induced alteration of sterol metabolism.

Animals↗
PubMed1983

Dietary ascorbic acid and hepatic mixed function oxidase activity in the guinea pig.

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.

Animals↗
PubMed1983

The influence of dietary fiber source on human intestinal transit and stool output.

Wheat bran ground to a coarse and fine particle size, purified cellulose and ethanol-extracted cabbage fiber, fed to 24 adult males during an 80-day metabolic trial, were examined for effects on intestinal transit time, laxation and stool composition. Brilliant blue, plastic pellets, polyethylene glycol (PEG)-4000 and Cr(III) mordanted onto isolated bran fiber were simultaneously administered for transit measurements. Intersubject variability in response to fiber source was highly significant for all transit and stool measurements. Only coarse bran or cellulose addition increased transit speed (decreased transit time) over basal rates. Grinding of bran significantly reduced fecal output because of reduced fecal water. Only subjects consuming cellulose or fine bran reported difficult or uncomfortable defecations. Though cabbage produced the smallest fecal output, stools had a high moisture content comparable to those obtained from coarse bran, which suggests a large microbial output in response to a fermentable substrate. Significant negative correlations were produced when changes in dry matter or cell wall intakes were regressed with Cr (III) transit. These findings suggest that the level of either food or fiber in the diet are variables that influence intestinal transit time and should be controlled in studies measuring it. Increases in fiber intake linearly increased fecal output of water and dry matter. Regression slopes were characteristic of each fiber source.

Adult↗
PubMed1981

Influence of chronic ascorbic acid deficiency and excessive ascorbic acid intake on bile acid metabolism and bile composition in the guinea pig.

The influence of chronic ascorbic acid (AA) deficiency and excessive ascorbate consumption on bile acid metabolism, liver and plasma cholesterol levels, hepatic microsomal cytochromes and biliary lipid composition was investigated. Male weanling guinea pigs were fed a cereal-based scorbutigenic diet supplemented with four levels of AA for 7 weeks: deficient, 15 and 30 mg/kg; control, 500 mg/kg; and excess, 20,000 mg/kg. Bile acid kinetic parameters were determined following the intraperitoneal administration of [24-14C] chenodeoxycholic acid. Dietary extremes of AA caused similar alterations in the parameters studied. Relative to the control group, the deficient and excess groups exhibited reduced cytochrome P-450 concentration, lower cholesterol 7 alpha-hydroxylase activity, lower bile acid turnover rate, prolonged bile acid half-life and increased plasma and liver cholesterol concentrations. Deficient and excess groups also exhibited lower biliary cholesterol saturation (i.e., increased bile acid-neutral sterol ratios) than controls. Urinary bile acid excretion was 2- to 3-fold higher in excess guinea pigs than in the other three groups. The data demonstrate the exceptional susceptibility of cholesterol 7 alpha-hydroxylase activity to alteration by dietary extremes of AA, resulting in marked inhibition of bile acid synthesis and elevation of cholesterol levels by both inadequate and excessive AA intake.

Animals↗
PubMed1975

Relationships of ascorbic acid to pregnancy, and oral contraceptive steroids.

The 1974 RDA is 60 mg per day for pregnant women and 80 mg per day for lactating women. In the present study an attempt was made to simulate this intake in the guinea pig and study reproduction performance in relation to guinea pigs fed chronically low and high levels. In animals that conceived and carried the young to term, all 3 dietary levels of ascorbic acid appeared to be adequate for maintaining viability of fetuses and of offspring, and for growth of offspring during the nursing period. The chronically low intake level was not adequate for growth after weaning. The control group was superior to the chronically low-intake group but inferior to the high-intake group in conceiving, producing litters, and carrying litters to term. The level of intake in the control group was inadequate to maintain tissue stores. Even the high intake was inadequate to maintain some tissues at saturation levels. The results suggest that the requirement for ascorbic acid during pregnancy and lactation has been markedly underestimated.

Adrenal Glands↗
PubMed1975

Oral contraceptives and ascorbic acid.

Plasma, leukocyte, and platelet ascorbic acid levels are decreased in women ingesting oral contraceptive steroids. Studies have shown that it is the estrogenic component of the oral contraceptive agents that is associated with the decresased ascorbic acid concentrations. Urinary excretion of ascorbic acid does not appear to be increased by the steroids. Although serum levels of copper are increased by estrogens and oral contraceptives, ascorbic acid catabolism does not appear to be increased (unpublished). Our preliminary data on tissue uptake of ascorbic acid suggest that changes in tissue distribution are one possible answer for the observed effects of the steroids on blood levels of ascorbic acid.

Adrenal Glands↗
PubMed1975

Hypertriglyceridemia in patients with chronic renal insufficiency.

The development of hypertiglyceridemia was studied in 38 patients who were at different deteriorative stages of chronic renal insufficiency, as measured by corrected creatinine clearance. Patients in the mild stages of chronic renal insufficiency showed a 53% decrease in postheparin lipolytic activity, and no change in plasma triglyceride levels. In the moderate and severe stages, plasmia triglycerides were significantly elevated but there was no further decrease in PHLA. Those patients undergoing chronic hemodialysis showed a further increase in plasma triglycerides and postheparin lipolytic activity decreased to near zero. Serum electrophoretic studies indicated that in the moderate and severe stages of chronic renal insufficiency, prior to initiating hemodialysis, the chylomicron and very low density lipoprotein fraction were elevated. In those patients receiving chronic hemodialysis hyperchylomicronemia was the predominant finding.

Cholesterol↗