T.K. Basu

Short-Term Effect of Zinc Sulphate on Plasma and Hepatic Concentrations of Vitamins A and E in Normal Weanling Rats

In normal weanling male rats, the intraperitoneal administration of zinc sulphate (ZnSO4) resulted in a decreased hepatic and an increased plasa concentration of vitamin A after 2 h. In an in vitro study, the vitamin A concentrations of liver homogenates were markedly increased when homogenized livers were treated with ZnSO4, ZnSO4, however, did not show any effect on plasma and liver concentrations of vitamin E. These results indicate that zinc may be specifically involved in mobilizing vitamin A from liver to the circulation of normal animals within a short period. The trace element, therefore, could be used only to treat cases of depressed vitamin A in plasma but also to treat hepatic toxicity from hypervitaminosis A.

A goitrogenic agent from millet (Pennisetum typhoides) in Darfur Province, western Sudan.

Serum samples from girls from an elementary school in Western Sudan with grades O, I and II/III goitre were examined for their thiocyanate, cysteine, thyroxine, TSH and T3 concentrations. The concentrations of thiocyanate in all girls was higher than that reported in the literature for Nigerians, but the concentrations of thiocyanate were nevertheless significantly elevated, and those of thyroxine significantly lowered in girls with grades I and II/III goitre as compared with grade O. There were no significant differences between any of the groups in the concentrations of cysteine or TSH and T3. The predominant staple food eaten in this area of Sudan is millet and evidence is produced that this contains a goitrogenic thionamide which could be a factor in causing the endemic goitre.

Effect of large doses of ascorbic acid on the mixed function oxidase system in guinea pig liver

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.

Effect of Corticosterone on the Plasma and Tissue Concentrations of Vitamin A in Rats

The administration of large doses of corticosterone to normal adult male rats resulted in a rapid loss of vitamin A from the plasma, liver, adrenals and thymus. Of the organs studied, the thymus appeared to be the most sensitive to treatment. The steroid-mediated depression of plasma and tissue contents of vitamin A was reversed when animals were treated with corticosterone in combination with vitamin A.

Effect of Protein/Energy Nutrition on Rat Plasma Corticosteroids and Liver Microsomal Hydroxylase Activity

Three groups of 24-day-old male Wistar rats were fed (a) a control diet containing 210 g/kg protein ad libitum (control) (b) a low protein diet consisting of the stock diet diluted with starch to contain 70 g/kg protein ad libitum (protein deficient) or (c) an amount of stock diet containing the same amount of protein as eaten by (b) but without starch (energy deficient). The low protein diet did not affect the ability of the animals to metabolize biphenyl and excrete it as 4-hydroxybiphenyl, or reduce the total activity of 4-hydroxylase per liver, whereas this was reduced by restricted amounts of the high protein diet. The low protein diet resulted in raised levels of corticosteroids in the plasma. It is concluded that the raised specific activity, and unchanged total amount of biphenyl 4-hydroxylase per liver of the low protein animals is an adaptation to the diet mediated by corticosteroids as exogenous corticosteroids were also found to increase the activity of this enzyme in normal animals.

Impairment of absorption of ascorbic acid following ingestion of aspirin in guinea pigs

A study was undertaken to investigate the interactions between aspirin and ascorbic acid in guinea pigs. Animals received by gastric intubation either a single dose of radiolabelled ascorbic acid alone or ascorbic acid with aspirin and the exhalation of CO2 was monitored for 400 min following administration. Animals receiving the vitamin only reached plasma peak levels within 90 min following administration while coadministration of the vitamin with aspirin, not only resulted in lower plasma peak levels, but also delayed their attainment until after 160 min. The bioavailability of ascorbic acid during the first 400 min was reduced by half following simultaneous administration of aspirin. The initial rate of exhalation of CO2 was decreased by 70% following coadministration of aspirin. These observations indicate that aspirin impairs the gastrointestinal absorption of ascorbic acid in guinea pigs, possibly by interfering with its active transport.

Effect of Dietary Substitution of Sucrose and its Constituent Monosaccharides on the Activity of Aromatic Hydroxylase and the Level of Cytochrome P-450 in Hepatic Microsomes of Growing Rats

The effect of dietary substitution of starch by sucrose, glucose, fructose or an equimolar mixture of glucose and fructose on the activity of biphenyl hydroxylase and the level of the major terminal mixed function oxygenase, cytochrome P-450, has been studied in hepatic microsomal preparations from growing rats. The substitution of sucrose for starch depressed the contration and total activity per liver of biphenyl 4-hydroxylase and the concentration, but not the total amount, of cytochrome P-450 in weanling rats. The absolute amount of these enzymes in whole liver was not, however, similarly depressed by the constituents of sucrose, namely glucose and fructose, either when given alone or in equimolar mixture. All these sugars, however, depressed the total activity of biphenyl 2-hydroxylase. The activity of biphenyl 4-hydroxylase in the liver of weanling rats, but not of adults, was reduced when the level of sucrose in the diet was reduced from 60 to 10%.

Effect of pharmacological doses of ascorbic acid on the hepatic microsomal haemoproteins in the guinea-pig

1. Ascorbic acid deficiency results in a reduction in the activity of the hepatic mixed function oxidase systems in the guinea-pig. In this study, male Dunkin-Hartley guinea-pigs were given 0, 50, 100, 200 or 300 mg ascorbic acid/d in two equal doses in buffered sucrose solution (200 g/l) for 4 d. Controls received an equal volume of sucrose solution. 2. A dose of 50 mg ascorbic acid/d resulted in a significant rise in the specific activities of both cytochromes P-450 and b5. At doses of 200 and 300 mg ascorbic acid/d the concentration of both haemoproteins was significantly lower than the control values. These effects were mirrored by total microsomal haem concentration. 3. These results suggest that when given in large doses, ascorbic acid ceases to act simply as a vitamin and should be considered a drug competing for substrates and cofactors with co-administered drugs and endogenous substrates such as cholesterol.

Evaluation of urinary alkaline ribonuclease activity in the assessment of subclinical malnutrition in weanling rats.

The sensitivity of the hydroxyproline (OHP)/creatinine (Cr) index and the free urinary alkaline ribonuclease activity as indices of nutritional status have been compared using rats as an experimental model. The results have revealed that the OHP/Cr index is a better biochemical parameter than the urinary alkaline ribonuclease activity for indicating a subclinical degree of malnutrition.