Effect of malathion, estradiol-17-beta and progesterone on ascorbic acid metabolism in prenatal rats and their pups.

The effects of prenatal exposure to 13.78 mg, 27.56 mg or 82.6 mg malathion/100 g body weight po from 6-13 d of gestation, to 1 microgram estradiol-17-beta/d/100g body weight or 4 mg progesterone/d/100 g body weight sc from 3-20 d of gestation, or to their various combinations on brain acetylcholinesterase activity and ascorbic acid metabolism were investigated in rat dams and pups. Brain acetylcholinesterase activity was taken as an index of toxicity. Significant inhibition of acetylcholinesterase from malathion exposure was further exaggerated by estradiol-17-beta, but was reversed by progesterone. Significant increases of ascorbic acid levels and L-gulonolactone oxidase was observed with malathion toxicity. Estradiol-17-beta decreased ascorbic acid levels and stimulated dehydroascorbatase, while progesterone had no significant effect on ascorbic acid levels or on enzyme activities.

Effect of castration on the metabolism of L-ascorbic acid in rat prostate.

An appreciable decrease in the contents of prostatic ascorbic acid and dehydroascorbic acid along with an increase in diketogulonic acid was seen in rats ten days after castration. Castration caused a decrease in the activities of such biosynthetic enzymes as L-gulono-gamma-lactone oxidase and D-glucuronolactone-delta-hydrolase with no significant alteration in the activity of L-gulono-gamma-lactone hydrolase in the rat prostate. The activity of dehydroascorbatase, one of the degrading enzymes was, however, found to be elevated in castration. The implication of these results has been discussed.

Studies on the possible mechanism of hydrazine action on ascorbic acid-metabolising enzymes.

The activities of enzymes associated with the synthesis and degradation of L-ascorbic acid were studied in hydrazine-treated rats supplemented with pyridoxine. The effects of hydrazine in vitro were also examined on these enzymes. The activity of liver D-glucuronoreductase was reduced in hydrazine-treated rats even after receiving pyridoxine in excess. But, the decreased activities of liver and kidney dehydroascorbatases in hydrazine-treated rats were reversed by pyridoxine supplementation. Hydrazine in vitro could not inhibit the activity of liver D-glucuronoreductase or L-gulonooxidase. The drug was also unable to inhibit in vitro the activity of liver and kidney dehydroascorbatases. Studies with dialyzed liver homogenates showed that the diminished activity of D-glucuronoreductase in the liver of hydrazine-treated rats was maintained even after dialyzing the tissue preparations. In contrast, the reduced activity of dehydroascorbatase in the liver of hydrazine-treated rats was abolished following dialysis of the liver preparations. It has been suggested that the diminished activity of liver D-glucuronoreductase after hydrazine treatment might arise from the reduced synthesis of enzyme protein, while the reduction in the activity of dehydroascorbatase following hydrazine treatment could be ascribed to depletion in vivo of pyridoxal phosphate and/or to the involvement of some dialyzable factors.

Tissue ascorbic acid and a liver dehydroascorbatase in guinea-pigs.

The extraction, partial purification and assay of a dehydroascorbatase from guinea-pig liver is described. There was no evidence that changes in dehydroascorbatase activity could account for the modified tissue ascorbic acid concentrations associated with aging or with the ingestion of fluoride, flavonoids or anthocyanin material.

Biochemical studies on polychlorinated biphenyl toxicity in rats: manipulation by vitamin C.

The effects of chronic polychlorinated biphenyl (PCB) compound toxicity on L-ascorbic acid metabolism in rats have been studied. PCB treatment brought about a depression in the activities of the enzymes L-gluonolactone oxidase and dehydroascorbatase along with an increased tissue levels and urinary excretion of L-ascorbic acid. PCB toxicity drastically disturbed the normal histological pattern of the liver cells and also significantly changed the hepatic lipid composition. L-ascorbic acid supplementation to the toxicated group of animals, although could not prevent the growth retardative effect of PCB, could afford a definite protection against the enzyme activity alterations and histological changes as caused by PCB toxicity.

Some studies on ascorbic acid metabolism in hydrazine-treated rats.

The metabolism of ascorbic acid was studied in hydrazine-treated rats. Hydrazine was administered i.p. at a dose of 1.28 mg/day (20% LD50) for each 100 g body weight for 7 days. Hydrazine administration at the present dose did not appear to have an effect on the total ascorbic acid level of liver, kidney, spleen and testis. The adrenal and plasma total ascorbic acid levels were, however, elevated. The activity of liver D-glucuronoreductase and that of liver and kidney dehydroascorbatases were diminished after hydrazine administration. The changes in the activities of liver enzymes were accompanied by a fall in the reduced ascorbic acid level and an elevation in the dehydroascorbic acid level. The uronolactonase activity of liver, on the other hand, remained independent of hydrazine treatment. It has been suggested that hydrazine treatment at the present dose reduced the biosynthesis of L-ascorbic acid from D-glucuronolactone as substrate. In spite of diminished synthesis, the normal level of total ascorbic acid in the liver of hydrazine-treated rats was maintained by reducing the degradation of L-ascorbic acid. The rise in the plasma total ascorbic acid level after hydrazine treatment was ascribed to reduced catabolism and urinary excretion of ascorbic acid, while the elevation in adrenal total ascorbic acid level might result from increased uptake of ascorbic acid by the gland from blood or from nonfunctional accumulation.

An explanation for the long duration of mydriatic effect of atropine in eye.

The mydriatic effect of topically applied 3H-atropine (2%) was compared in the pigmented rabbits (black fur and dark brown irides) and nonpigmented (albino) atropinesterase-negative rabbits. The duration, t1/2, of the mydriatic effect in the nonpigmented and pigmented rabbit was 43.5 and greater than 96 hours, respectively. At hour 96, the tissue 3H-atropine in the pigmented iris was greater than that in the nonpigmented iris by the factor of eight. The longer duration of mydriatic effect in the pigmented iris is explained by the slow release of the bound drug from the pigment onto the muscarinic receptors.