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Biomedical subjects

P Galtier

Publications and source records attributed to P Galtier.

At least 91 records · Page 5Linked to original sources
PubMed1989

Comparative effects of T-2 toxin and diacetoxyscirpenol on drug metabolizing enzymes in rat tissues.

The effects of T-2 toxin and diacetoxyscirpenol on tissue drug-metabolizing enzymes in young male rats were compared. Mycotoxicoses were produced by daily oral administration of toxins at 1.0 mg/kg body weight for 1, 4 or 8 days. Many hepatic, renal and pulmonary oxidative and conjugative enzymes were measured in animals killed 24 hr following the last administration. The effects of the two trichothecene mycotoxins were generally similar. In liver the decrease in microsomal and cytosolic proteins paralleled the decline in total plasma proteins or the increase in plasma GOT activity. Hepatic microsomal cytochrome P-450 decreased in rats receiving trichothecenes for 8 days. This effect was more marked when aminopyrine, benzphetamine, ethylmorphine and ethoxycoumarin dealkylations or aniline and benzopyrene hydroxylations were measured. p-nitrophenol glucuronyltransferase activity was enhanced in animals receiving at least one administration of trichothecenes, whereas there was no change in conjugation to glutathione or acetate. In other tissues, there was no change in any renal enzymes whereas a significant rise in pulmonary monooxygenase was observed in T-2 toxin administered to rats for 4 or 8 days.

Animals↗
PubMed1989

Comparative incidence of experimental fascioliasis on corticosteroid pharmacokinetics in sheep.

1. The kinetics of intravenously administered prednisone (0.5 mg/kg) and methylprednisolone hemisuccinate (4 mg/kg) were compared in two groups of four young male sheep before and regularly after experimental infestation with 150 metacercariae of Fasciola hepatica and 5 or 7 weeks following a flukicidal treatment administered post-infection at week 25. 2. Parasitic pathology was ascertained by clinical observation and by the increase in plasma antibodies directed against liver flukes. 3. The disposition of prednisone was altered with a significant decrease of plasma clearance occurring from eleven weeks after infection onwards. This change was parallel to an increase in the mean residence time of prednisone and of its major metabolite (prednisolone). 4. The same parasitic burden provoked only a slight decrease in the elimination half-life of methylprednisolone alcohol when its hemisuccinate ester was administered.

Animals↗
PubMed1988

A comparative study of some oxidative and conjugative drug metabolizing enzymes in liver, lung and kidney of sheep.

1. The comparative distribution of cytochrome P-450 monooxygenase system, glucuronyltransferase, glutathione S-transferase and N-acetyltransferase was studied in the liver, lung and kidney of young male sheep. 2. The sheep liver was characterized by a lack in glutathione S-transferase activity with isoniazid as substrate. 3. The oxidative drug metabolizing enzymes of lung were generally close to those of liver; benzphetamine N-demethylase and ethoxycoumarin O-deethylase were even found to be higher in lung (213 and 148%, respectively). 4. Pulmonary conjugative and both renal oxidative and conjugative systems accounted only for 9-38% of hepatic corresponding enzymes. 5. The enzyme determination in various sampling sites of the three organs, demonstrated the homogeneous distribution of all investigated monooxygenases and transferases in liver, lung and kidney of sheep.

Animals↗
PubMed1988

Incidence of a subclinical fascioliasis on antipyrine clearance and metabolite excretion in sheep.

1. The pharmacokinetics of i.v. antipyrine (25 mg/kg) used as a model compound, were determined in young male sheep, before and each month after an oral infestation by 150 metacercariae of Fasciola hepatica, and 8 weeks following a flukicidal treatment. 2. The parasitic pathology was ascertained by the clinical observation of animals and the increase in plasma antibodies directed against liver flukes. 3. A significant decrease in the total plasma clearance of the drug occurred by week 4 to 16, and a 1.7 fold increase in mean residence time occurred by week 12 post-infection. 4. Urinary excretion of antipyrine metabolites was determined before and 8 weeks following the infestation. 4-Hydroxyantipyrine was the major urinary metabolite and its excretion was decreased by 30% in infected sheep, whereas there was no change in the excretion of norantipyrine, 3-hydroxymethylantipyrine or unmetabolized drug. 5. It is concluded that the impairment of antipyrine clearance in the course of fascioliasis could be related to the decrease in liver microsomal cytochrome P-450-dependent mono-oxygenases observed in sheep with a similar parasitic burden.

Animals↗
PubMed1987

Fasciola hepatica: liver enzymes in rats and interaction with chemical inducers.

Adult male rats were sorted into control and infected groups, the latter receiving an oral dose of 20 metacercariae of Fasciola hepatica. In Weeks 3 and 6 after infection, some rats received phenobarbital or 3-methylcholanthrene which induced drug metabolizing enzymes. The parasitic pathology was ascertained by clinical observation of the rats and at autopsy. Hepatic microsomal cytochrome P-450 content was significantly decreased in infected rats compared to untreated phenobarbital treated groups. In all infected rats, the simultaneous increase in cytosolic calcium and decrease in cytosolic glutathione corresponded to oxidative cell injury occurring in the course of fascioliasis. Both arylamine acetyltransferase (EC 2.3.1.5.) and glutathione transferase (EC 2.5.1.18) activities were decreased in all newly infected and 6 week infected groups. Fascioliasis did not alter the substrate related uridine diphosphate glucuronosyltransferase activities (EC 2.4.1.17) of any rat group.

Animals↗
PubMed1987

Determination of ivermectin in milk by high performance liquid chromatography.

A sensitive and specific high performance liquid chromatographic technique is described for the determination of ivermectin in milk. Milk samples (1 ml) were extracted with organic solvent (iso-octane and acetonitrile) and then chromatographed using reversed phase system. Specificity of the assay was confirmed by the use of mass spectrometry. After an subcutaneous administration of ivermectin (0.2 mg/kg) in a cow, ivermectin was detected in milk for about three weeks and over this period milk and plasma concentration were of the same order of magnitude.

Animals↗
PubMed1987

Pharmacokinetics of sulphobromophthalein, lidocaine and indocyanine green in the course of subclinical fascioliasis in sheep.

The pharmacokinetics of three drugs proposed for the assessment of liver function: sulphobromophthalein (BSP), lidocaine and indocyanine green (ICG) were determined in sheep four, eight, 12, 16 and 24 weeks after their infestation by an oral administration of 150 metacercariae of Fasciola hepatica. The disposition of BSP was altered by a significant decrease in its total plasma clearance from eight weeks after infection onwards. This change could be related to the low values of the elimination rate constant consistent with a reduced liver cytosolic conjugation of the dye to glutathione. Lidocaine pharmacokinetics were unaffected by parasitism and the only effect on ICG was an increased volume of distribution consistent with the liver hypertrophy caused by the subclinical fascioliasis.

Animals↗
PubMed1986

Sulfoxidation of albendazole by a cytochrome P450-independent monooxygenase from rat liver microsomes.

The in vitro biological oxidation of albendazole to albendazole sulfoxide by rat liver microsomes has been studied. This reaction corresponds to a NADPH-dependent enzymatic system, characterised by Km and Vm values of 53.6 microM and 0.59 nmole/mg protein per min. The rate of sulfoxidation by liver microsomes of rats treated with phenobarbital, B-naphthoflavone, Aroclor 1254 and 3-methylcholanthrene was not increased. SKF 525A and metyrapone did not inhibit albendazole sulfoxidase. Thiobenzamide and tranylcypromine decreased sulfoxidation to 48 and 52% of control values. The inhibition by tranylcypromine was competitive. Purified flavin adenine dinucleotide (FAD)-containing monooxygenase from hog liver microsomes catalysed sulfoxidation of albendazole (V = 0.52 nmole/nmole enzyme per min). The present data demonstrate that sulfoxidation of albendazole in the rat liver is not catalysed by a cytochrome P450-dependent monooxygenase and suggest that albendazole is a substrate for FAD-containing monooxygenase (FMO).

Albendazole↗
PubMed1986

In vitro sulfoxidation of albendazole by ovine liver microsomes: assay and frequency of various xenobiotics.

The in vitro biological oxidation of albendazole to its pharmacologically active sulfoxide and its sulfone by ovine liver microsomes has been studied. Sulfoxidation (maximal rate = 0.412 nmole/min/mg of protein, Michaelis constant = 185 X 10(-6) M) was 107 times more potent than formation of albendazole sulfone. The sulfoxidation corresponds to a reduced nicotinamide-adenine dinucleotide phosphate-dependent enzymatic system characterized by a pH optima value around 8. Flavin adenine dinucleotide-containing monooxygenase could be responsible for this S-oxygenation because of the strong inhibitory effect of methimazole. Albendazole sulfoxidase is inhibited competitively by the related anthelmintic drug fenbendazole (inhibitory constant = 243 X 10(-6) M) and noncompetitively by chlorpromazine (inhibitory constant = 135 X 10(-6) M). At high concentration, chloramphenicol, erythromycin, nalidixic acid, and hexobarbital are less active inhibitors, whereas dexamethasone acetate significantly enhances the reaction which is not inhibited by either carbon monoxide, griseofulvin, imidazole, phenylbutazone, or proadifen.

Albendazole↗
PubMed1985

Incidence of experimental fascioliasis on hepatic disposition of [3H]tetracycline and [14C]rafoxanide in rats.

[7-3H]Tetracycline and [carbonyl-14C]rafoxanide were injected intravenously into anesthetized controls and rats in which experimental fascioliasis had been induced by 20 Fasciola hepatica metacercariae. The biliary excretion (1 and 3 h, respectively) of the radioactivity consisted of approximately 4% of the administered dose. In 4-week infested rats, biliary excretion of [3H]tetracycline and hepatic levels of radioactivity were decreased, whereas bile flow did not vary and plasma clearance of the antibiotic was significantly decreased in comparison with control animals. These differences could be the result of the fascioliasis-induced decrease in the hepatic uptake of tetracycline and the limited active transport for its output into bile canaliculi. No change in [14C]rafoxanide disposition was shown in infested rats.

Animals↗
PubMed1985

Induction of drug metabolizing enzymes in the liver of rats infested with Fasciola hepatica.

Adult, male rats were infected with 20 metacercariae of Fasciola hepatica given orally, other rats were left untreated. Five weeks after infestation, some animals received phenobarbitone, 3-methylcholanthrene, beta-naphthoflavone or Arochlor 1254, to induce liver drug metabolizing enzymes. Fascioliasis provoked decreases in aminopyrine N-demethylase, aniline hydroxylase, the mutagenic activity of cyclophosphamide and cytochrome P-450 concentration in untreated or phenobarbitone or Arochlor pretreated rats. In contrast, cytochrome b5, NADPH cytochrome c reductase, ethyoxycoumarin O-deethylase and the enzymatic activation of ethidium bromide were not affected by fascioliasis whatever pretreatment was given. Fascioliasis decreased liver drug metabolizing enzymes which were specifically induced by both phenobarbitone and Arochlor, this could be due to either the specific action of toxic excretions of flukes or to the particular localization of tissue damage within the liver lobule.

Animals↗
PubMed1984

Comparative incidence of oral ochratoxicosis and aflatoxicosis on the activity of drug-metabolizing enzymes in rat liver.

Mycotoxicosis has been produced in the rat by daily oral administrations of ochratoxin A (1.5 mg/kg/day) or aflatoxin B1 (1 mg/kg/day). Hepatic microsomal cytochrome P-450 and b5 contents and many phase I and II biotransformation systems have been measured in the course of ochratoxicosis (4 to 15 dosings) and aflatoxicosis (1 to 8 dosings). In case of ochratoxicosis, decreases in cytochrome P-450 level, aminopyrine demethylase and aniline hydroxylase activities were observed in rats receiving 15 administrations of the toxin. Aflatoxicosis induced more severe decreases in cytochrome P-450, aminopyrine demethylase and ethoxycoumarin deethylase following 8 daily gavages. In the two studies, there was no significant change in activities of liver phase II biotransformation enzymes.

7-Alkoxycoumarin O-Dealkylase↗