摘要:

1. Rainbow trout were dosed with prochloraz by i.p. injection of sprayed food pellets. Cytochrome P-450, two P-450-dependent activities, and two conjugase activities were measuredin vitroin microsomal or cytosolic fractions2. Prochloraz increased cytochrome P-450 in liver, intestine, and pyloric caeca: maximum response occurred at 30-100 mg/kg i.p. In cold conditions, this increase persisted for more than 8 days after injection.3. Hepatic 7-ethoxycoumarin-O-dealkylase (ECOD) and 7-ethoxyresorufin-O-dealkylase (EROD) were inhibited by prochloraz except in one assay in warm water where they increased. In intestine and pyloric caeca, ECOD and EROD were not detected, even when cytochrome P-450 was increased.4. UDP-glucuronosyltransferase (1-naphthol as substrate) was unchanged or inhibited after prochloraz dosing.5. Glutathione-S-transferase (o-dinitrobenzene as substrate), was unchanged or inhibited by prochloraz.6. The measured level of enzymic activities was the result of induction and inhibition by prochloraz residues. Variations in basal activities and perhaps in prochloraz interactions were due to temperature acclimatization.

ISSN:0049-8254    

DOI:10.3109/00498258909034671

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

1. Epicainide is a new potent antiarrhythmic agent, metabolized differently in rats and man.2. In rats, the aromatic part of the molecule (the two phenyl rings linked to the quaternary carbon atom) undergoes metabolic attack by the mono-oxygenases. The hydroxy and methoxy-hydroxy metabolites are predominant and are excreted in urine and bile both as free and conjugated forms.3. In contrast, the aromatic moiety of epicainide remains unchanged in man. It is the ethylpyrrolidine ring which is mainly attacked, resulting in the expectedN-deethylation, subsequent oxidation of the pyrrolidine moiety, and reduction or hydrolysis of the amide function.4. A preliminary kinetic analysis of epicainide -in man reveals a linear open 2-compartment model. The radioactivity recoveries confirm the absence of any accumulation of the drug in the organism.

ISSN:0049-8254    

DOI:10.3109/00498258909034672

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

1. Oral administration of deoxynivalenol (DON) to control rats resulted in the appearance of a de-epoxy metabolite in urine and faeces.2. When DON was administered to rats treated with antibiotics to deplete their gut microflora there was very little excretion of radioactivity as the de-epoxy metabolite in faeces or urine.3. Incubation of DON with a strictly anaerobic preparation of gut contents resulted in the progressive appearance of de-epoxy DON during a 24 h incubation period.4. Incubation of DON with liver homogenate did not result in the appearance of the de-epoxy DON metabolite.5. These results indicate that the presence of de-epoxy DON in rat excreta, following the oral administration of DON, is the result of metabolism by micro-organisms in the gut.

ISSN:0049-8254    

DOI:10.3109/00498258909034673

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

1. 3,4,5,6-Tetrahydro-2H-azepine is an intermediate in the enzyme-catalyzed conversion of 1,6-diaminohexane to 6-aminohexanoic acid and its corresponding lactam, caprolactam, by mammalian liver aldehyde oxidase.2. Identification of metabolites was based on analysis by gas chromatography-mass spectrometry and confirmed by comparison with the properties of authentic standards.3. The results indicate that the cell differentiating agent hexamethylene bisacetamide is converted into 1,6-diaminohexane, and its metabolism therefore involves diamine oxidase.4. The metabolic fate of 1,6-diaminohexane is similar to that of putrescine and cadaverine in that a cyclic imine is an intermediate in the formation of metabolites with ring (lactam) and chain (amino acid) structures.

ISSN:0049-8254    

DOI:10.3109/00498258909034674

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

1. Administration of benzidine (100mg/kg, i.p.) to bile duct-cannulated rats led to a sustained excretion of metabolites in bile which, following glucuronide hydrolysis, were mutagenic toSalmonella typhimuriumstrain TA98.2. When the biliary metabolites were re-infused into the duodena of a further group of rats, enterohepatic circulation of mutagens was indicated by extensive re-excretion of biliary mutagens in the recipients.3. Furthermore, in mouse host-mediated mutagenicity assays, both i.p. injection of benzidine (100mg/kg) and intracaecal administration of rat biliary metabolites of benzidine produced a mutagenic response inSalmonella typhimuriumstrain TA98 cells isolated from the liver.4. The results indicate that enterohepatic circulation adds to the biological persistence of reactive metabolites of benzidine and may contribute to the carcinogenicity of this aromatic amine.

ISSN:0049-8254    

DOI:10.3109/00498258909034675

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

1.14C-Flocoumafen, administered to Japanese quail as a single oral or i.p. dose, was rapidly and extensively eliminated in excreta; most was eliminated within 24h. Extensive metabolism of the rodenticide was seen, with at least 8 metabolites detected; unchanged flocoumafen comprised 9% dose. The elimination kinetics and metabolic profiles were qualitatively similar after oral and i.p. dosing.2. The major metabolites (60% dose) were labile toβ-glucuronidase, liberating aglycones with identical chromatographic mobilities to those of the unchanged flocoumafen isomers.3. Radioactivity was retained mostly in the liver, largely as unchanged flocoumafen associated with the mitochondrial and microsomal fractions. Elimination of radioactivity from most tissues was biphasic with an initially rapid depletion (5 days) followed by a slow terminal elimination phase. The elimination half life from liver was>100 days.4. Livers of quail receiving extended dietary exposure to flocoumafen at 5, 15 and 50ppm had concentrations of flocoumafen (1.0nmol/g) that were independent of dose, indicating a capacity-limited binding site. These hepatic concentrations were similar to those after a single oral dose and were also similar to those in rats. The data indicate the presence in quail liver of a saturable high affinity flocoumafin binding site with similar characteristics and capacity to that in the rat.5. The selective toxicity of flocoumafen to rats (highly toxic) and quail (moderately toxic) appears to arise from differences in metabolism rather than from anticoagulant binding in the liver. When hepatic binding sites of rats are saturated anticoagulant action becomes lethal, whereas quail are able to survive and extensively metabolize the compound.

ISSN:0049-8254    

DOI:10.3109/00498258909034676

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

1. Appreciable penetration of radioacticity occurred through rat skin following percutaneous administration of14C-flocoumafen. At 7 days after dosing 12% of the administered radioactivity remained at the site of application, while 25% was located in the liver as unchanged flocoumafen.2. Excretion of flocoumafen metabolites via the urine accounted for 10% dose over the 7 day experiment, this is some 30-fold greater than that seen after a single oral dose.3. Unchanged flocoumafen comprised the major product detected in faeces. Biliary elimination was a very minor route of excretion and did not account for all of the unmodified flocoumafen present in faeces.4. Considerable amounts of unchanged flocoumafen found associated with the contents of the large intestine after intraperitoneal administration to rats fitted with biliary fistulae indicates that, in the intact rat, flocoumafen enters the intestine by a non-biliary intestinal excretion mechanism.

ISSN:0049-8254    

DOI:10.3109/00498258909034677

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

1. Interspecies variability in the metabolism of pentachlorophenol (PCP) was investigated by exposing rainbow trout, fathead minnows, sheepshead minnow, firemouth, and goldfish to water-borne14C-PCP for 64 h.2. The amounts of metabolites in bile and exposure water were species-dependent; all of the metabolites excreted into the water were sulphate conjugates while bile was enriched in glucuronide conjugates.3. Biliary excretion accounted for less than 30% of the total PCP metabolites.4. Biliary metabolites alone were a poor indication of the metabolites produced and of the major routes of elimination.

ISSN:0049-8254    

DOI:10.3109/00498258909034678

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

1. The major biliary metabolite of 2,4-dinitrotoluene (2,4-DNT) in male Wistar rat was 2,4-dinitrobenzyl alcohol glucuronide and the minor metabolites were 2,4-dinitrobenzyl alcohol, 2,4-dinitrobenzaldehyde, 2-acetylamino-4-nitrotoluene, 4-amino-2-nitro(2-amino-4-nitro)benzyl alcohol sulphate, 2,4-dinitrobenzoic acid, 2,4-diacetylaminobenzoic acid and 2-amino-4-nitrobenzoic acid.2. 2,4-Dinitrobenzyl alcohol, 2,4-dinitrobenzaldehyde, 2,4-dinitrobenzyl alcohol glucuronide and 4-amino-2-nitro(2-amino-4-nitro)benzyl sulphate were excreted in the bile of male Wistar rat dosed with 2,4-dinitrobenzyl alcohol.3. 2,4-Dinitrobenzaldehyde, 2,4-dinitrobenzyl alcohol, 2,4-dinitrobenzyl glucuronide, 4-amino-2-nitro(2-amino-4-nitro)benzyl alcohol sulphate and 2,4-diacetylaminobenzoic acid were excreted in the bile of male Wistar rat dosed with 2,4-dinitrobenzaldehyde.4. These results indicate that the common biliary metabolites of 2,4-DNT, 2,4-dinitrobenzyl alcohol and 2,4-dinitrobenzaldehyde are 2,4-dinitrobenzyl alcohol and its glucuronide, and 2,4-dinitrobenzaldehyde, and suggest the enterohepatic circulation of 2,4-dinitrobenzaldehyde in the metabolism of 2,4-DNT.

ISSN:0049-8254    

DOI:10.3109/00498258909034679

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

ISSN:0049-8254    

DOI:10.3109/00498258909034680

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor