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Biomedical subjects

D V Parke

Publications and source records attributed to D V Parke.

At least 163 records · Page 9Linked to original sources
PubMed1980

The effects of sodium carbenoxolone on the stability of cellular membranes.

Various mechanisms have been proposed for the mode of action of carbenoxolone, most of which contribute to improving the mucosal defence and the protective mucus barrier. The incorporation of many sugars into the glycoprotein fraction of gastric mucus of man, ferret and rat is increased by carbenoxolone and the turnover of gastric epithelial cells in the mouse has been shown to decrease after carbenoxolone treatment. The gastric mucosal cell membrane together with the subcellular endoplasmic reticulum and lysosomes contain large amounts of phospholipids and cholesterol. The protective role of gastric mucus and the development of gastric lesions is partly dependent on the activity of the mucosal cell lysosomes. Evidence is presented to show that carbenoxolone at pharmacological doses has a significant stabilising effect on lysosomal membranes and also on artificial phosphatidylcholine:cholesterol liposomes.

Animals↗
PubMed1979

Metabolic oxidation of the ethynyl group in 4-ethynylbiphenyl.

1. 4-Ethynylbiphenyl undergoes extensive metabolism in the rat and the rabbit, involving aromatic hydroxylation and oxidation of the ethynyl group. No metabolites containing the intact ethynyl group were detected. 2. In the rat unchanged 4-ethynylbiphenyl was concentrated initially in the adipose tissue. No other tissues accumulated significant amounts of radioactivity. 3. The major metabolites were the same in both the rat and the rabbit, namely 4'-hydroxybiphenyl-4-ylacetic acid (90-95% of dose) and biphenyl-4-ylacetic acid (2-10% of dose). 4. Excretion was slower in the rat than in the rabbit, probably because of greater biliary and faecal excretion in the rat. Biliary excretion and enterohepatic circulation of biphenyl-4-ylacetic acid and 4'-hydroxybiphenyl-4-ylacetic acid were demonstrated in the rat.

Acetylene↗
PubMed1979

The tissue disposition and urinary excretion of cadmium, zinc, copper and iron, following repeated parenteral administration of cadmium to rats.

The effect of repeated parenteral administration of cadmium (0.75, 1.5 and 3.0 mg/kg) on tissue disposition and urinary excretion of cadmium, zinc, copper and iron has been studied in the male rat. Cadmium, zinc and copper accumulated in liver and kidney, but the concentration of iron did not alter significantly. The kidney weight relative to body weight showed a dose-related increase in weight of 25--65%. Excretion of cadmium in the urine increased directly with dosage and the increase was most significant when kidney damage had probably occurred. Administration of cadmium also resulted in dose-related increases in the urinary excretion of zinc, copper and iron. The cadmium concentration of blood increased with dosage of cadmium, and the plasma concentrations of zinc and copper were also raised but plasma iron concentration was diminished.

Animals↗
PubMed1979

Inhibition of thiabendazole metabolism in the rat.

1. A single oral dose of desmethylimipramine (80 mg/kg) administered to rats inhibited the hepatic microsomal hydroxylation of thiabendazole (45%), aniline (30%), biphenyl (30%) and ethylmorphine (15%) in vitro at 5 h after dosage; there was no decrease in cytochrome P-450 or b5. 2. A single oral dose of ethoxyquin (200 mg/kg) to rats inhibited the hepatic microsomal hydroxylation of thiabendazole (65%), aniline (40%) and biphenyl (40%) in vitro at 1 h after dosage; inhibition was less at 5 h. There were no changes in the contents of cytochromes P-450 and b5. 3. The max. plasma concn. of thiabendazole occurred 2--4 h after oral dosing (50--200 mg/kg) to rats. Thiabendazole (100 mg/kg) administered orally 30 min after oral ethoxyquin (400 mg/kg) or thiabendazole (200 mg/kg) administered orally 30 min after oral desmethylimipramine (80 mg/kg) delayed absorption of the thiabendazole and resulted in markedly markedly decreased plasma concentration of the anthelmintic. 4. Simultaneous administration of ethoxyquin (300 mg/kg) potentiated the anthelmintic effect of thiabendazole (750 mg/kg) on the helminth parasite, Nematospiroides dubius, in the mouse. Desmethylimipramine showed no similar potentiation.

Animals↗
PubMed1979

Metabolism of phenformin in the rat and guinea-pig.

1. Following administration of [2'-14C]phenformin to rat and guinea pig, the guinea-pig showed a slower rate of excretion of radioactivity than the rat, together with a slower rate of metabolism, which may partly explain the increased pharmacological response of the guinea-pig to the drug. 2. The rat eliminated 26% of an intraduodenal dose of [2'-14C]phenformin (20 mg/kg) in the bile in 6 h compared to 6% in the guinea-pig. 3. The rat excreted large amounts of 4-hydroxyphenformin (free and conjugated with glucuronic acid) and also some unchanged phenformin, but the extent of metabolism varied with dose and route of administration. 4. The guinea-pig excreted no 4-hydroxyphenformin after an oral dose (25 mg/kg) and only a small amount after i.p. administration (12.5 mg/kg). After oral administration, guinea-pig urine contained an unidentified metabolite, and its glucuronide, which may be a product of aliphatic C- or N-hydroxylation and which accounted for 47% of the 24 h urinary radioactivity (17% of the dose). Guinea-pig faeces contained an unidentified metabolite which had similar chromatographic properties to the novel urinary metabolite.

Administration, Oral↗
PubMed1979

Effect of diet on the metabolism and toxicology of drugs.

The human organism is continuously exposed to a variety of xenobiotics, as drugs, pesticides, food additives and many environmental contaminants, all of which are potentially toxic. The body metabolizes these highly reactive chemicals to pharmacologically-inert compounds, which are readily eliminated from the body. This process of deactivation is dependent on nutritional status. Malnutrition, almost invariably, leads to a reduced capacity to deactivate these exogenous materials with consequent increase in toxicity.

Animals↗
PubMed1978

The metabolism of shikimate in the rat.

In the rat, shikimate was metabolized and excreted as hippurate, hexahydrohippurate, 3,4,5,6-tetrahydrohippurate, t-3,t-4-dihydroxycyclohexane-r-1-carboxylate and c-3,t-4-dihydroxycyclophexane-r-1-carboxylate, conjugates of catechol and CO2. The metabolism was entirely dependent on various initial microbial transformations in the gut, metabolite formation being suppressed in animals pretreated with antibiotics. Shikimate was not metabolized by mammalian tissues, and products of microbial metabolism were excreted either unchanged or after further biotransformation in the animal tissues.

Animals↗
PubMed1978

The anaerobic dechlorination of trichlorofluoromethane by rat liver preparations in vitro.

Incubation of trichlorofluoromethane with a liver microsomal fraction and an NADPH generating system under anaerobic conditions produced a metabolite dichlorofluoromethane, characterised by gas chromatography and mass spectrometry. The metabolic reaction was carried out by liver microsomes from the mouse, rabbit, hamster and rat and was increased by phenobarbitone pre-treatment. The formation of dichlorofluoromethane in vitro was enhanced by the addition of FMN, but partially inhibited by the presence of air, oxygen, SK&F 525-A, metyrapone and carbon tetrachloride and totally inhibited by carbon monoxide. The consumption of NADPH in the reaction was greater than could be accounted for by the production of dichlorofluoromethane indicating the possible formation of other metabolic products. It is suggested that trichlorofluoromethane interacts with the reduced form of cytochrome P-450 at the oxygen binding site and a possible mechanism for its subsequent reductive dechlorination is proposed.

Aerosol Propellants↗