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Biomedical subjects

G Goerz

Publications and source records attributed to G Goerz.

At least 199 records · Page 11Linked to original sources

[Influence of chloroquine on the hexachlorobenzene-induced porphyria. Investigations in the skin, liver, and urine (author's transl)].

Rats were fed with a diet containing hexachlorobenzene (HCB) for about 60 days. At this time the porphyria was manifst as shown by significantly elevated porphyrins. Thereafter, chloroquine (CQ) was additionally given over a period of at lest 6 weeks. At the end of the experiment the urinary porphyrin excretion and the porphyrin content in lijver and skin were diminished in HCB-CQ-treated animals by about 50% compared to the HCB controls. The relative porphyrin distribution pattern was not influenced by CQ. In a further investigation the prophylactic effect of CQ could be demonstrated. Rats given CQ simultaneously from the beginning of the HCB feeding showed a significantly delayed onset of porphyria. It is concluded from our results that CQ does not only form complexes with porphyrins during the treatment of th HCB porphyria. We rather assume an effect of CQ on the metabolism of iron.

Animals↗

Inducibility of drug-metabolizing enzymes in the rat skin.

The influence of systemic application of chemically unrelated drugs and xenobiotics (phenobarbital (PB), rifampicin (Rifa), pregnenolone-16 alpha-carbonitrile (PCN) and 3-methylcholanthrene (MC) on drug metabolizing enzymes was investigated in the skin of rats of both sexes. The results were compared with those obtained in the liver. PB, Rifa and PCN induced the aryl hydrocarbon hydroxylase (AHH) in the skin though to a lesser extent than MC. The basal enzymic activity as well as the inducibility were considerably lower in the skin than in the liver. The activity of cytochrome c reductase was similar in all rats independently from the pretreatment. Only slight sex differences were noted: generally, the activity was higher in males. Cytochrome P-450 content of the skin could not be detected as well as various dealkylation activities.

Animals↗

Effects of intravenous and intracutaneous bacillus Calmette-Guérin application on the drug-metabolizing system of the liver.

Both single intravenous and repeated intracutaneous injections of bacillus Calmette-Guérin (BCG) resulted in alteration of the hepatic microsomal drug-metabolizing enzymes of the rat liver. The cytochrome P-450 content was not significantly altered; its activity (ethoxycoumarin O-dealkylation) was inhibited in both the intravenous and intracutaneous group. The arylhydrocarbon-hydroxylase and aminopyrine-demethylase activities were also diminished; decrease of cytochrome-c-reductase activity was noted after intravenous application only. Comparison of the results for the intravenous and intracutaneous application routes respectively showed qualitative and quantitative differences. The inhibitory effects of BCG treatment on the drug-metabolizing enzymes of the rat liver can only partly be explained by changes in the cytochrome P-450 system. These findings might lead to reconsideration of dosage of drugs in cancer (malignant melanoma) patients treated by combined chemoimmunotherapy.

Animals↗

Enzymic and electrophoretic characterization of the hexachlorobenzene-induced cytochrome P-450 in the liver of rat.

1. Hexachlorobenzene induces the cytochtome P-450 system in rat liver microsomes. The catalytic activity of the enzyme towards various substrates (dealkylation of 7-ethoxycoumarin, hydroxylation of biphenyl and NADPH-dependent reduction of cytochrome c) corresponds to that obtained in animals treated with a mixture of phenobarbital and benzpyrene. 2. Electrophoretic separation of the partly purified hexachlorobenzene-induced cytochrome P-450 in sodium dodecyl sulphate polyacrylamide gels exhibits a protein pattern similar to that found in microsomes from rats treated with phenobarbital plus benzpyrene.

Animals↗

[Cytochrome P-450 dependent enzymatic activity in the liver of patients with porphyria cutanea tarda (author's transl)].

In the liver of 12 patients with porphyria cutanea tarda (PCT) the following parameters were measured: protein-content, NADPH-cytochrome c-reductase, 7-ethoxycoumarin-deethylase. The results were compared with the findings of patients with chronic liver disease (chronic hepatitis or cirrhosis) and patients without any liver affection. In addition the in vitro inhibition of 7-ethoxycoumarin-deethylase by metyrapone (phenobarbital induced cytochrome P-450) or naphthoflavone (benzo[a]pyrene induced cytochrome P-448) was estimated. No differences were found between the various groups. It is assumed that the induction of the mixed function monooxygenases is not an essential condition for the development or the persistence of the human porphyria cutanea tarda.

7-Alkoxycoumarin O-Dealkylase↗

[Influence of p-amino-benzoic acid on the hexachlorobenzene induced porphyria in the rat (author's transl)].

The effect of p-amino-benzoic (PAB) acid on the experimental hexachlorobenzene (HCB) induced hepatic porphyria of female Wistar rats was determined under different conditions: Neither a simultaneous HCB-PAB application (prophylactic administration) nor the PAB application after manifestation of the HCB-porphyria (therapeutic administration) influenced significantly the excretin of urinary porphyrins or precursors (porphobilinogen or 5-amino-levulinic acid). PAB application decreased the cytochrome P-450 content in the liver of the rats whereas HCB incuded enzymatic activity of this monooxygenase measured by the O-dealkylation of 7-ethoxycoumarin was not diminished by PAB application. The glycine concentration and the glycine content of rat livers were not decreased by the simultaneous HCB-PAB treatment in contrast to PAB controls. These findings are discussed and the conclusion is drawn that there might be different types of human porphyria cutanea tarda. The predominently exogenously induced PCT in men and the HCB induced porphyria in rats cannot be influenced by PAB application.

4-Aminobenzoic Acid↗

[Erythropoietic protoporphyria].

Erythropoietic protoporphyria (EEP) is the most frequently found erythropoietic porphyria in men. This inborn error of heme metabolism with autosomal dominant mode of inheritance is based on a deficiency of ferrochelatase. This defect leads to an increase for protoporphyrins predominantly in the red cells. Under the influence of sun light, especially UV-A, photohemolysis occurs and the content of protoporphyrin in the tissue increases. This is associated with acute sun burn like skin lesions, which usually clear up completely. Persistent skin lesions are seen in form of hyalinosis like infiltrations of the most intensively light exposed skin areas in some patients. Associated symptoms might be: gallstones or rarely a cirrhosis of the liver. Treatment with photoprotective ointments and especially carotinoids (beta-carotene, canthaxanthine) is very effective and only in some rare cases this symptomatic therapy fails. Prognosis of the disease is good. Only a few patients died of the associated hepatic failure.

Carotenoids↗

[Modern internal therapy of skin diseases (author's transl)].

Modern internal therapy of skin diseases is based on a knowledge of pharmacology and biochemical pharmacology. The importance of the cytochrome P 450 system and its changes during treatment are referred to. Standard treatment in dermatology is not discussed but the literature is mentioned here. Treatment with glucocorticosteroids and non-steroidal anti-inflammatory substances are discussed in detail. The treatment of porphyria cutanea tarda with chloroquine shows good success. The results of carotinoid therapy of erythropoietic protoporphyria and non-porphyrin induced photodermatoses are debated.

Anti-Inflammatory Agents↗

Effect of hexachlorobenzene on enzymes of the steroid metabolism in rat liver.

Adult female Wistar rats were fed with a diet containing 0.05% hexachlorobenzene. On the 60th day of this treatment the specific activities of NADPH: delta 4-3-oxosteroid-5 alpha-reductase and the 3-hydroxysteroid dehydrogenases in rat liver microsomes were diminished compared to control rats. The cytoplasmatic 5 beta-reduction was higher in HCB treated rats than in control rats. These alterations of the steroid metabolism lead to increased formation of 5 beta-H-steroids which are known to be inducers of the porphyrin biosynthesis.

3-Hydroxysteroid Dehydrogenases↗

Induction of the hepatic microsomal and nuclear cytochrome P-450 system by hexachlorobenzene, pentachlorophenol and trichlorophenol.

The application of hexachlorobenzene (HCB), pentachlorophenol (PCP) and 2,4,5-trichlorophenol (TCP) to female rats led to an induction of both the microsomal and the nuclear cytochrome P-450 system in the liver. The increase of th mixed-function hydroxylase activities examined (7-ethoxycoumarin deethylase, 7-ethoxyresorufin deethylase, NADPH-dependent cytochrome c reductase, aminopyrine demethylase, benzpyrene hydroxylase) did not correlate strictly with the cytochrome P-450 content. Depending on the inducers and the substrates used, the content and the activity of the cytochrome P-450 were essentially smaller in the nuclei than in the microsomes. It was striking that in the nuclei those activities (benzpyrene hydroxylase, 7-ethoxyresorufin deethylase, 7-ethoxycoumarin deethylase) were preferably induced which can be attributed to the methyl-cholanthrene-induced form of the cytochrome P-450 (cytochrome P-448). These results suggest, also in the light of findings of other authors, the induction of different species of cytochrome P-450 in the nuclei and microsomes.

7-Alkoxycoumarin O-Dealkylase↗