The effect of molybdenum on ascorbic acid metabolism in rats

1. The effect of dietary molybdenum on the growth rate and also on ascorbic acid metabolism in rats was studied. An excess of dietary molybdenum resulted in growth retardation and loss of weight. Tolerance to molybdenum was affected by the nature of the molybdenum salt administered. 2. Molybdenum ingestion altered certain aspects of ascorbic acid metabolism in rats. The conversion of d-glucuronolactone into l-ascorbic acid in vitro and the oxidative breakdown of l-ascorbic acid by liver enzymes decreased with high molybdenum intakes. The activity of liver uronolactonase was slightly inhibited. The activities of l-gulonate dehydrogenase and l-gulonate decarboxylase were not affected appreciably. 3. Molybdenum supplementation of the control diet resulted in an increase in ascorbic acid content of spleen and adrenal gland, and in a marked decrease in the urinary excretion of ascorbic acid and glucuronic acid. The implications of these findings are discussed.     

Impaired ascorbic acid metabolism in streptozotocin-induced diabetic rats

Ascorbic acid (AA) metabolism in streptozotocin (STZ)-induced diabetic rats was determined by examining urinary excretion, renal reabsorption, reductive regeneration, and biosynthesis of AA at 3 and 14 days after STZ administration. AA concentrations in the plasma, liver, and kidney of the diabetic rats were significantly lower than those of controls on d 3, and decreased further as the diabetic state continued. Hepatic AA regeneration significantly decreased in the diabetic rats on d 3 in spite of increased gene expressions of AA regenerating enzymes and was further reduced on d 14. Hepatic activity of L-gulono-gamma-lactone oxidase, a terminal enzyme of hepatic AA biosynthesis, also decreased significantly on d 3 and decreased further on d 14. Urinary excretion of AA was significantly increased on d 3, with an increase in urine volume but no change in gene expressions of renal AA transporters (SVCT1 and SVCT2). Urinary excretion of AA was normalized on d 14. The results suggest that impaired hepatic and renal regeneration, as well as increased urinary excretion and impaired hepatic biosynthesis of AA, contributed to the decrease in AA in plasma and tissues of STZ-induced diabetic rats.     

Changes in catecholamine metabolism by ascorbic acid deficiency in spontaneously hypertensive rats unable to synthesize ascorbic acid

We have previously reported the establishment of a novel rat strain, SHR-od, with both spontaneous hypertension and a defect of ascorbic acid biosynthesis. Blood pressure in mature SHR-od fed an ascorbic acid-supplemented diet is over 190-200 mmHg, while it decreased to around 120 mmHg at 4-5 weeks after the cessation of ascorbic acid supplementation. With regard to possible mechanisms of blood pressure lowering, we focused on catecholamine synthesis in adrenal glands, since catecholamine is a major factor for blood pressure regulation and ascorbic acid is a co-factor of dopamine beta-hydroxylase (DBH) in catecholamine biosynthesis. Male SHR-od (25-week-old) and normotensive ODS rats with a defect in ascorbic acid biosynthesis (25-week-old) were fed a Funabashi-SP diet with or without ascorbic acid (300 mg/kg diet) for 28 days or 35 days. In SHR-od, systolic blood pressure (191 +/- 6 mmHg) began to decrease from day 21 in the ascorbic acid-deficient group, whereas no significant difference was found in ODS rats. In spite of significant lowering of blood pressure, no significant differences were found in catecholamine levels in serum, adrenal glands and brain on day 28. On day 35, however, urinary excretion of norepinephrine and epinephrine in the ascorbic acid-deficient SHR-od were higher at 490% (P < 0.05) and 460% (P < 0.05) of the respective control. Serum catecholamine concentrations and the adrenal catecholamine content tended to be higher in the ascorbic acid-deficient SHR-od than the control of SHR-od and reached to similar level in ODS rats. The administration of ascorbic acid (intraperitoneal injection, 60 mg ascorbic acid/kg body weight, once a day) to the ascorbic acid-deficient SHR-od restored blood pressure to the range 180-190 mmHg within two days. These findings indicate that ascorbic acid deficiency affects catecholamine metabolism in the adrenal glands of SHR-od in response to blood pressure lowering, suggesting catecholamines are not involved in the mechanism for the remarkable reduction in blood pressure in response to ascorbic acid deficiency.     

Effects of protein malnutrition and ascorbic acid levels on drug metabolism

The duration of action of drugs (or other environmental chemicals) is dependent on their rate of metabolic deactivation and elimination from the body. Termination of activity is achieved either through excretion of the drug via the kidney and bile or, more commonly, through metabolic deactivation by enzymes of the liver and other tissues. In recent years, it has become increasingly obvious that nutritional status is one of the major factors capable of modifying the pharmacological effect of drugs. Numerous studies have indicated that the process of drug metabolism may be affected by acute starvation, undernutrition, protein nutrition, and deficiencies of minerals, vitamins, and lipids. Although most of the evidence concerning the effects of nutrition on the metabolism of drugs has been derived from studies on experimental animals, there is significant fragmentary human data to show that the same effects may occur in man. This paper will discuss the influence of nutritional status with particular references to protein and ascorbic acid on the metabolism of foreign compounds including drugs. The interrelationships of nutrition and the metabolism of drugs are an important consideration in view of the widespread recurrence of primary malnutrition in the developing countries, and of secondary malnutrition in more affluent societies, especially in debilitated chronically ill patients, in postoperative patients, and in those whose dietary manipulations are carried out in weight-reducing regimens. The effects of nutrition on drug metabolism may be viewed as an extension of the search for one of the environmental factors that modify drug action.     

Effects of dietary protein type on the response of lipid metabolism to orotic acid in rats

The effects of orotic acid supplementation to casein, egg protein, soy protein and wheat gluten diets on the lipids of liver and serum were compared. When orotic acid was added, the contents of total lipids and triacylglycerol in the liver of the casein group were significantly higher or tended to be higher than those of the other three dietary groups. Dietary orotic acid had no effect on the food intake. The liver weight, and liver total lipids, triacylglycerol, cholesterol and phospholipids were increased or tended to be increased by the addition of orotic acid. The serum triacylglycerol level was decreased by the addition of orotic acid to either the casein or soy protein diet. Thus, the response to liver lipid accumulation induced by orotic acid feeding depended on the dietary protein type.     

Effect of different doses of ascorbic acid on thyroid activity in rats at different levels of dietary protein intake.

Rats, which can synthesize vitamin C, react similarly to graded doses of ascorbic acid as guinea pigs. Low doses of ascorbic acid stimulate and high doses inhibit the thyroid activity of rats which are supplied with normal and high percentages of protein. The stimulatory effect of low doses of ascorbic acid on hyperactive thyroid of high protein fed animals is additive. Ascorbic acid has no significant effect on the thyroid of low protein fed animals (deficient diet supplied for 21 days). In the initial stages of protein deficiency (deficient diet supplied for 11 days) the effectiveness of vitamin C on thyroid of rats was still significant. Deiodinase enzyme activity of peripheral tissues is markedly reduced in animals supplied with 2% of protein for 21 days, but this effect is less intense in animals supplied with 2% of protein for 11 days.     

The effect of dietary ascorbic acid and alpha-tocopherol on fecal mutagenicity

The effect of supplemental ascorbic acid and alpha-tocopherol on fecal mutagenicity was examined in 2 studies involving 20 healthy human donors aged 22-55 years. The vitamins were given at a dose of 400 mg daily each. The mutagen was extracted from individual frozen feces samples with dichloromethane, and assayed with Salmonella Typhimurium tester strain TA100 without microsomal activation. In the first study, with a single donor on a controlled diet, the fecal mutagenicity decreased (P less than 0.001) on treatment to 21% of control. In the second study, with 19 donors on free-choice diets, the mutagenicity in producers on treatment decreased (P less than 0.01) to 26% of control. Addition of ascorbic acid and alpha-tocopherol directly to feces led to no change in mutagenicity. Antioxidants in the diet may have a role in lowering the body's exposure to endogenously produced mutagens.     

The influence of maternal nicotine exposure on neonatal lung metabolism. Protective effect of ascorbic acid.

The aim of the present study was to establish whether ascorbic acid supplementation (1 mg/kg/body mass/day) during pregnancy and lactation will prevent the effect of maternal nicotine exposure (1 mg/kg body weight/day) on neonatal lung carbohydrate, DNA and protein metabolism. The data show that the adult lung ascorbic acid content was reduced by 76% after exposure to nicotine. In contrast, maternal nicotine exposure during pregnancy and lactation has no effect on neonatal lung ascorbic acid content. However, ascorbic acid supplementation during pregnancy and lactation prevented the adverse effects of maternal nicotine exposure on neonatal lung carbohydrate, DNA and protein metabolism.     

Biosynthesis and metabolism of ascorbic acid in plants

The biosynthesis of L‐ascorbic acid in plants differs from that encountered in ascorbic acid‐synthesizing animals. Enzymic details are sparse, but in vivo studies with tracers clearly establish the stereochemical detail of both processes. Examples of each process are found in separate classes of algae. Plants utilize L‐ascorbic acid as the carbon source for the biosynthesis of two important plant acids, oxalic acid and L‐tartaric acid. Here, cleavage of L‐ascorbic acid between carbons 2 and 3 releases the 2 and 4 carbon intermediates. A second L‐tartaric acid‐synthesizing process peculiar to vitaceous plants, i.e., grape, cleaves ascorbic acid between carbons 4 and 5. The physiological significance of these metabolic interconversions is discussed. Other metabolic processes such as the oxidation/reduction properties of L‐ascorbic acid are also considered.