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G Koss

Publications and source records attributed to G Koss.

36 records · Page 2Linked to original sources
PubMed1986

Screening for the ability of hexachlorobenzene metabolites to decrease rat liver porphyrinogen carboxy-lyase.

In order to examine inhibitory effects of hexachlorobenzene metabolites on the hepatic porphyrinogen carboxylyase activity, rat liver cytosol was incubated with uroporphyrinogen III and chlorinated phenols, thiophenols, thioanisoles and benzenes. Then, the occurrence of hepta-, hexa-, penta- and tetracarboxyporphyrinogen = coproporphyrinogen (measured as porphyrins) was determined. Inhibitory effects were exerted by tetrachlorohydroquinone, pentachlorophenol, pentachlorothiophenol, 1,2,3,5- and 1,2,4,5-tetrachlorobenzene. Other compounds including hexachlorobenzene which was tested for comparative reasons did not impair uroporphyrinogen decarboxylation. In the presence of tetrachlorohydroquinone, uroporphyrinogen merely was decarboxylated to hepta- and hexacarboxyporphyrinogen. Under the influence of the other 4 compounds with inhibitory effects, pentacarboxyporphyrinogen and coproporphyrinogen were formed additionally. Coproporphyrinogen formation was inhibited completely by tetrachlorohydroquinone, while pentachlorophenol diminished its formation by about 50% and pentachlorothiophenol, 1,2,3,5- and 1,2,4,5-tetrachlorobenzene by less than 10%.

Animals↗
PubMed1982

Metabolic fate of hexabromobenzene in rats.

To study the metabolic fate of hexabromobenzene (HBB) in female rats, the substance was administered in oral doses of 16.6 mg/kg body weight every other day for 2 weeks and the animals' excreta were examined for metabolites. Unchanged HBB, pentabromobenzene, oxygen- and sulphur-containing metabolites were detected in feces and urine. The sulphur-containing substances contained free mercapto groups except for the presence in feces of a methylmercapto derivative. The amount of sulphur-containing metabolites was estimated to be 15 times greater than that of oxygen-containing compounds. The relative proportions of the unchanged compound and its metabolites in the excreta were about 1:4.

Animals↗
PubMed1982

Enteral absorption and biotransformation of the food additive octyl gallate in the rat.

Following oral administration of 14C-labelled octyl gallate in a single dose of 15 mg/kg to female rats, only 20-30% of the radioactivity administered was detected in the tissues, while 60-80% of the dose was found in the contents of the gastro-intestinal tract up to 12 hr after administration. Isotope dilution analysis demonstrated the presence of the unchanged ester in the tissues. In the liver, the highest concentration of the ester demonstrated was 1.6 micrograms/g. in a rat killed 10 min after treatment. In the 24 hr following ip administration of labelled octyl gallate, about 91% of the administered radioactivity was recovered. Most of this was in the form of metabolites, only 9% being accounted for as unchanged ester.

Animals↗
PubMed1981

Biotransformation and porphyringogenic action of hexachlorobenzene and its metabolites in a primary liver cell culture.

Hexachlorobenzene (HCB) is metabolized in a primary culture of chick embryo liver cells and causes porphyrin accumulation within 24 h after administration. The HCB-metabolites, pentachlorothiophenol (PCThP), pentachlorobenzene (PeCB) and pentachlorophenol (PCP) identified in liver cell culture are already known from long-term experiments with rats. The pattern of accumulated porphyrins is comparable with the pathological porphyrin pattern observed in oral feeding studies with warm blooded laboratory animals. Protein bound radioactivity was found in cell cultures treated with [14C] HCB. Addition of the monooxygenase-inhibitor piperonyl butoxide or ascorbic acid decreased the irreversible binding of 14C-metabolites. The results show that biotransformation of HCB fulfils an essential role in the onset of porphyria. Since none of the main HCB-metabolites could induce a pathological porphyrin pattern, a reactive intermediate capable of reacting with glutathione or thiol-groups of uroporphyrinogen decarboxylase (UROG-D) is believed to be responsible for the inhibition of UROG-D. The chick embryo liver cell system may be considered as a useful and sensitive system for studying the metabolism of xenobiotics in relation to their toxicity.

Animals↗
PubMed1980

Uroporphyrinogen decarboxylase deficiency in experimental chronic hepatic porphyria.

During hexachlorobenzene feeding of rats the following biochemical signs of a chronic hepatic porphyria developed: porphyrinuria with increase of uro- and hexacarboxyporphyrin, hepatic prophyrin accumulation of uro- and heptacarboxyporphyrin and a diminished activity of uroporphyrinogen decarboxylase in the liver, but nut in the red cells. During the 5.3 days of the intoxication the behaviour of metabolite constellation and enzyme activities was inverse. Hexachlorobenzene porphyria in rats is a pathobiochemical model of chronic hepatic prophyria, which in man becomes clinically manifest as porphyria cutanea tarda.

Animals↗
PubMed1979

Rat liver alterations after chronic treatment with hexachlorobenzene.

Groups of female rats were treated orally with 0.5, 2.0, 8.0, and 32 mg/kg hexachlorobenzene twice a week for 203 days. The liver content of hexachlorobenzene was found to be dose-dependent. In the animals treated with the highest dose the concentration was 273 mug/g hexachlorobenzene. In the fresh and fixed hepatic tissue of the treated animals pink fluorescence was observed. Electron microscopy revealed a dose dependent enlargement of all hepatocytes due to proliferation of the SER in the centrolobular area or to increased glycogen deposits (beta- or alpha-particles) and SER in the intermediary and periportal area. Numerous porphyrin deposits and siderosomes, intimate disorganisation and moderate dislocation of the RER and a moderate enlargement of bizarre-sharped mitochondria were recognized. The relationship between porphyrin crystals and mitochondria on the one hand and between SER and glycogen deposits on the other is discussed.

Animals↗
PubMed1979

Studies on the toxicology of hexachlorobenzene. IV. Sulphur-containing metabolites.

After administration of hexachlorobenzene rats excrete sulphur-containing conjugates from which pentachlorothiophenol can be split off. In the present study we describe the identification of pentachlorothiophenol and pentachlorothioanisol in the livers of animals treated with hexachlorobenzene. In order to clarify the further fate of these two substances, we administered them to rats, and isolated the conversion products excreted in the urine and feces. The metabolites of pentachlorothiophenol and pentachlorothioanisol are excreted in both conjugated and free form. From extracts of the excreta, we isolated tetra- and trichlorobenzene with two or three sulphur-containing substituents on the ring, analogous compounds in which thiol groups were converted into sulphoxide and sulphone groups, as well as analogous compounds with a phenolic oxygen in addition to sulphur, and sulphur-containing compounds in which clorine was replaced by hydrogen. Following administration of the sulphoxide and of the sulphone of pentachlorothioanisol under analogous conditions, pentachlorothiophenol and pentachlorothioanisol and their metabolites were detected in the excreta of the animals. No evidence was obtained that the parent compounds are excreted in the unchanged form.

Animals↗
PubMed1976

Studies on the toxicology of hexachlorobenzene. II. Identification and determination of metabolites.

Female rats were dosed intraperitoneally with 14C-hexaxhlorobenzene. The drug was administered on 2 or 3 occasions. The total doses amounted to 260 and 390 mg/kg 14C-hexachlorobenzene, respectively. Urine and feces from the animals were collected over a period of 4 weeks after the first injection. Both excreta and some tissues of the animals were examined for their content of radioactivity and for hexachlorobenzene and its metabolites. Gas chromatography, isotope dilution analysis, and combined gas chromatography-mass spectrometry were used to identify the metabolites of hexachlorobenzene. In urine pentachlorophenol, tetrachlorohydroquinone, and pentachlorothiophenol were present as major metabolites. One of the isomers of tetrachlorothiophenol was present as a minor metabolite. In the feces pentachlorophenol and pentachlorothiophenol only were identified. At the end of the experiment, carbon-14 excreted with urine and feces amounted to 7% and 27%, respectively, of the radioactivity administered. More than 90% of carbon-14 excreted in urine was contained in the major metabolites. In the feces about 30% of the excreted radioactivity was bound to metabolites and about 70% was contained in the unchanged drug, while in the tissues of the animals only pentachlorophenol was detected in measurable amounts, accounting for 10% of label in blood and less than 0.1% of carbon-14 determined in body fat. Total radioactivity contained in the metabolites detected in the animal body and in the excreta at the end of the experiment accounted for about 16% of the administered radioactivity.

Animals↗
PubMed1976

Hexachlorobenzene porphyria in rats as a model for human chronic hepatic porphyrias.

1. Hexachlorobenzene porphyria in the rat provides a suitable experimental model of the stages of development of human chronic hepatic porphyria. Just as in chronic hepatic porphyria in man, the development of experimental HCB porphyria in the rat can be divided into several stages. 2. The findings in this study indicate that porphyrins increase in the urine, liver, kidney, and spleen, and to a lesser degree in the serum, with uroporphyrin and heptacarboxylic porphyrin predominating. 3. In contrast to the distribution of porphyrin accumulation in the various organs, clear evidence of a uroporphyrinogen decarboxylase defect was found only in the liver. Formation of uroporphyrin and heptacarboxylic porphyrin by homogenized HCB kidney tissue did not deviate significantly from that by control kidney. The defect could not be unequivocally evaluated in the spleen because the spleen, like the red cells, normally forms considerable amounts of uroporphyrin from porphobilinogen, which were increased only a few times over in synthesis by the HCB spleen. 4. Isomer studies provide no evidence for an additional uroporphyrinogen cosynthase defect.

Aminolevulinic Acid↗
PubMed1975

Studies on the toxicology of hexachlorobenzene. I. Pharmacokinetics.

In female rats dosed orally with 14C-hexachlorobenzene the extent of intestinal absorption of carbon-14 has been found to be dependent on the form of application. When the substance was given as a solution in oil about 80% of the dose administered was absorbed, but when given as an aqueous suspension only 6%. In animals treated with 14C-hexachlorobenzene dissolved in oil, all tissues contained radioactivity. Highest levels were found in adipose tissue, lowest in blood and muscle. Peak values of radioactivity were reached between 2 to 5 days after application. Elimination was studied after intraperitoneal application of 4 mg/kg14C-hexachlorobenzene dissolved in oil. Two weeks after administration, 34% of the radioactivity administered was recovered in the feces and 5% in urine. About 80% of carbon-14 excreted in feces and about 4% in urine was contained in the unchanged drug. This indicates that biodegradation of hexachlorobenzene in the rat is not insignificant. No radioactivity was detected in the expired air.

Adipose Tissue↗