Influence of phenobarbital and TCDD on the hepatic metabolism of TCDD in the dog

Summary The influence of phenobarbital and TCDD pretreatment on the formation and biliary excretion of TCDD-metabolites following single doses of³H-TCDD was investigated. Without pretreatment, 24.5% of the absorbed³H-TCDD dose was excreted in the bile within 110 h. Phenobarbital did not influence this rate, whereas a single dose of 10 g of unlabeled TCDD/kg b.wt nine days earlier resulted in a doubling of the amount of radioactive material eliminated in the bile (47.4%).     

Accumulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin from soil and nutrient solution by bean and maize plants

Summary Maize and bean plants grown on soil polluted with³H-2,3,7,8-tetrachlorodibenzo-p-dioxin (³H-TCDD) accumulated the toxin in the aerial parts progressively with the time and with the soil contamination. Plants in hydroponic solution polluted with³H-TCDD accumulated the toxin in the aerial parts in the light and not in the dark; the concentration of TCDD accumulated was not proportional to the surface area of plant organs; the distribution of³H-TCDD in the leaves suggested that TCDD was translocated through the vessels to the aerial parts by the transpiration stream.     

A microbial metabolite of TCDD

Summary In the present study we describe the occurrence of a metabolite of TCDD, which arose in several microbial cultures after long term incubation. The polar metabolite amounted approximately 1% of the input material, and was found to be a hydroxylated derivative of TCDD.The work was supported by a grant from the Swiss Federal Government to R.H. and M.P. We thank Dr K. Grob, GC-Laboratory ETH Zürich, Dübendorf, Switzerland, for providing the highly inert column used in this work, and H.-R. Buser, Swiss Federal Research Station, Wädenswil, Switzerland, for his help in the analysis of the¹⁴C-TCDD.     

Effects of dosage and cadmium pretreatment on the binding of cadmium in rat bile.

The effects of dosage and of cadmium pretreatment on the binding of cadmium in rat bile were studied. With increasing dose a higher cumulative biliary excretion of Cd was observed and a higher percentage of the Cd was excreted in a low-molecular-weight form. On the other hand, after cadmium pretreatment, a decrease in the cumulative biliary excretion of cadmium was observed but a greater percentage of that excreted into the bile was bound to high molecular weight compounds.     

Effects of dosage and cadmium pretreatment on the binding of cadmium in rat bile

Summary The effects of dosage and of cadmium pretreatment on the binding of cadmium in rat bile were studied. With increasing dose a higher cumulative biliary excretion of Cd was observed and a higher percentage of the Cd was excreted in a low-molecular-weight form. On the other hand, after cadmium pretreatment, a decrease in the cumulative biliary excretion of cadmium was observed but a greater percentage of that excreted into the bile was bound to high molecular weight compounds.     

Structure elecidation of mammalian TCDD-metabolites

Summary Thin layer and gas chromatographic examination of the bile of dogs which were given tritium-labelled TCDD revealed the presence of several polar biotransformation products. The structure of 5 phenolic metabolites was elecidated by combined gas chromatography-mass spectrometry. A metabolic breakdown scheme for TCDD in the dog is proposed.     

Studies on the in vitro binding of D-penicillamine to cholestyramine

Summary Adsorption of D-penicillamine to cholestyramine depends on the amount of the resin, the pH and the presence of other compounds such as bile salts. In the usual drug to resin ratio (150 mg D-penicillamine and 4–8 g cholestyramine per single dose) the percentage of D-penicillamine adsorbed to cholestyramine was about 10% of the applied dose; Bile salts (10 mmoles/1) inhibited this small adsorption by 87%.     

Isoprenaline, modifications of the turnover of ATP in the perfused rat heart]

5 hrs after a single sub-cutaneous injection of the drug in a dose of 5 mg/kg, the ATP concentration was reduced by 15%, the incorporation of 14C adenine was augmented by 20% and the turnover of ATP was accelerated: the reduction of specific radioactivity attained 16%, 75 mn after the period of marquage, instead of 7% in the control hearts. When the drug was added to the perfusion fluid, there was no supplementary reduction of the ATP concentration and the action on the nucleotide turnover only existed if the ATP level was reduced by a pretreatment: the reduction of specific radioactivity then attained 24% after 75 min. of perfusion.     

The biliary excretion of [3H] lysergic acid diethylamide in Wistar and Gunn rats.

The biliary excretion of [3H] LSD was studied in Wistar and homozygous Gunn rats. In Wistar rats approximately 46% of the given dose was recovered from bile in 2.5 h whilst in the homozygous Gunn rat 26% was recovered in the same time period. In both strains the main metabolites were glucuronides.     

The biliary excretion of [3H] lysergic acid diethylamide in Wistar and gunn rats

Summary The biliary excretion of [³H] LSD was studied in Wistar and homozygous Gunn rats. In Wistar rats approximately 46% of the given dose was recovered from bile in 2.5 h whilst in the homozygous Gunn rat 26% was recovered in the same time period. In both strains the main metabolites were glucuronides.     

Biliary excretion and metabolism of14C cimetidine following oral administration to male and female rats

Summary In rats, the bile is not a major route of excretion of cimetidine or its metabolites, since only 10% of the¹⁴C associated with an oral dose of labelled cimetidine was excreted in the bile during 8 h after dosing.     

Influence of phenylbutazone on bile flow in the rat

Summary Phenylbutazone, a well-known enzyme inducer, at a dose of 80 mg·kg^–1 once daily for 8 days increases liver weight and bile flow expressed per g of liver (p<0.01). The bile salt secretory rate is not increased.     

Effect of the extracts from Aristolochia indica Linn. on interception in female mice.

The crude petroleum ether, chloroform and alcoholic extracts from the roots of Aristolochia indica (Linn.) showed 100% interceptive activity in mature female mice at the single dose of 100 mg/kg body wt. The follow-up studies with the chloroform extract showed the most significant effect in the basic part and two acidic fractions at the single dose levels of 50 mg/kg body wt. No toxic effect was observed at the dose levels used.     

Time-dependence of estradiol effects on protein synthesis in the rat neurohypophysis.

The incorporation of 3H-leucine into neurohypophyseal proteins was measured in vitro, 24 h after the administration of a single dose of estradiol (0.3 mug) to castrated female rats. Estradiol treatment caused a significant increase of 3H-leucine incorporation into proteins of the posterior lobe. The effects of estradiol depended largely upon time injection. Rats injected at 06.00 h, i.e., at the end of the dark period exhibited a 74% increase in protein synthesis, whereas rat injected at 14.00 h, i.e., at the middle of the light period only showed a 30% of increase.     

Absorption of double labeled (glycerol 3H-linoleic acid 14C) native bile by phosphatidylcholines]

Double-labeled bile ([U. 3H glycerol] [1. 14C linoleic acid])--in which about 70% of labeling 14C and 80% of labeling 3H of total lipids were borne by phosphatidylcholines (PC), (isotopic ratio of these PC was equal to 1)--was introduced into the duodenum of test Rats, some of them with a bile fistula. As low amounts of the hydrolysis products of biliary PC were found in the intestinal lumen, a higher hydrolysis must occur further (brush border, enterocyte ?) because, in the mucosa, the highest labeling 14C was present as triglycerides and PC have an isotopic ratio 3H/14C higher than 1. As in the lumen the isotopic ratio 3H/14C of PC was higher than 1 and increased with the time elapsed, this finding suggests that mucosal PC were added to biliary PC (secretion or desquamation ?) unless these modifications were due to luminal micro-organisms. As test Rat bile was poorly labeled a very weak enterohepatic circulation of biliary diunsaturated PC may exist.     

Degradation of 2,3,7,8-tetrachlorodibenzo-p-dioxin in organic solvents by gamma ray irradiation

Summary The effect of gamma ray irradiation on 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) dissolved in organic solvents is described; TCDD is degradated with the loss of 1 or more chlorine atoms.Gammatom, Via 24 Maggio, 14, I-22070 Guanzate, Como, Italy.     

Choleretic and cholestatic effects of infused bile salts in the rat.

In rats, at low infusion rates taurocholate (TC), taurochenodeoxycholate (TCDC) and taurodeoxycholate (TCD) each produced an increase in bile flow of 20-50%. However, at high infusion rates (5-20 mumoles min-1kg-1) the cholestatic effects of the bile salts were revealed and the relative toxicity of the bile salts was seen to be TDC greater than TCDC greater than TC.     

Neurotoxicity by the dividing administration of critical dose of phosvel

Phosvel, an organophosphorus insecticide, produces delayed neurotoxicity in hens. A change in the toxicity, and in the residue of insecticide in the fat, were observed when the critical dose which was demonstrated in the case of a single dose was subdivided.     

Neurotoxicity by the dividing administration of critical dose of phosvel

Summary Phosvel, an organophosphorus insecticide, produces delayed neurotixicity in hens. A change in the toxicity, and in the residue of insecticide in the fat, were observed when the critical dose which was demonstrated in the case of a single dose was subdivided.     

Effect of the extracts fromAristolochia indica Linn. on interception in female mice

Summary The crude petroleum ether, chloroform and alcoholic extracts of the roots ofAristolochia indica (Linn.) showed 100% interceptive activity in mature female mice at the single dose of 100 mg/kg body wt. The follow-up studies with the chloroform extract showed the most significant effect in the basic part and two acidic fractions at the single dose levels of 50 mg/kg body wt. No toxic effect was observed at the dose levels used.The authors are thankful to Mr.P. P. Ghosh Dastidar, Medicinal Chemistry Division for the plant extracts. Thanks are also due to Indian Council of Medical Research and Council of Scientific and Industrial Research for granting scholarships to two of them (B.C. and A.D.) and to Prof.R. N. Chakravarti, Director of the Institute for encouragement.