Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Regine Kahl is active.

Publication


Featured researches published by Regine Kahl.


Toxicology | 1984

Synthetic antioxidants: Biochemical actions and interference with radiation, toxic compounds, chemical mutagens and chemical carcinogens☆

Regine Kahl

Biological actions of 4 commonly used synthetic antioxidants--butylated hydroxyanisole, butylated hydroxytoluene, ethoxyquin and propyl gallate--on the molecular, cellular and organ level are complied. Such actions may be divided into modulation of growth, macromolecule synthesis and differentiation, modulation of immune response, interference with oxygen activation and miscellaneous. Moreover, an overview of beneficial and adverse interactions of these antioxidants with exogenous noxae is given. Beneficial interactions include radioprotection, protection against acute toxicity of chemicals, antimutagenic activity and antitumorigenic action. Possible mechanisms of the antitumorigenic action of antioxidants are discussed. This discussion is centered around antioxidant properties which may contribute to a modulation of initiation-related events, especially their ability to interfere with carcinogen metabolism. The beneficial interactions of antioxidants with physical and chemical noxae are contrasted to those leading to unfavorable effects. These include radiosensitization, increased toxicity of other chemicals, increased mutagen activity and increased tumor yield from chemical carcinogens. At present, the latter one can most adequately be characterized as tumor promotion at least in the case of butylated hydroxytoluene. It is concluded that current information is insufficient to promote expectations as to the use of antioxidants in the prevention of human cancer.


Toxicology and Applied Pharmacology | 1979

Induction of rat hepatic epoxide hydratase by dietary antioxidants

Regine Kahl; U. Wulff

Abstract Supplementation of rat diet with butylated hydroxytoluene (BHT), butylated hydroxyanisole, or ethoxyquin resulted in increased liver epoxide hydratase activity. The increase was obvious at 0.1% and amounted to 200–400% at 0.5%. Increased activity was accompanied by increased proportion of the epoxide hydratase band in SDS polyacrylamide gels, indicating induction of the enzyme. Ethoxycoumarin deethylase activity and cytochrome b5 concentrations were moderately elevated while cytochrome P-450 concentrations and aryl hydrocarbon hydroxylase activity remained at control levels. Preferential inhibition of monooxygenase activity by metyrapone and not 7,8-benzoflavone, as well as increased affinity of the reduced cytochrome P-450 for metyrapone as a ligand, indicated that the cytochrome P-450 population after BHT treatment was similar to that found after phenobarbital treatment. The antioxidants used in this study had no in vitro effect on epoxide hydratase activity and inhibited monooxygenase activity only in phenobarbital-stimulated microsomes but not in 3-methylcholanthrene-stimulated microsomes. Combined treatment with dietary antioxidants and intraperitoneally administered 3-methylcholanthrene resulted in marked induction of epoxide hydratase activity while the 3-methylcholanthrene-mediated increase in aryl hydrocarbon hydroxylase activity was partially depressed. Covalent binding of tritiated benzo[a]pyrene to calf thymus DNA was less effectively catalyzed by liver microsomes from animals fed antioxidants. The depression of covalent binding was marked after combined treatment with antioxidants and 3-methylcholanthrene. The shift in the microsomal enzyme pattern caused by antioxidants may be related to their inhibitory effects on chemical carcinogenesis.


Biochemical Pharmacology | 1974

Influence of pyridine and some pyridine derivatives on spectral properties of reduced microsomes and on microsomal drug metabolizing activity

Hans G. Jonen; Bernd Hüthwohl; Regine Kahl; Georg F. Kahl

Abstract Addition of pyridine, 3-(3-pyridyl)-propanol, reduced metyrapone and some other pyridine derivatives to dithionite reduced rat liver musomes results in the formation of a six banded spectrum with absorption maxima at 425, 446, 527, 539, 555 and 568 nm. With metyrapone as the ligand, a 425 nm band can only be observed during development of the spectrum. The ratio of the two Soret bands depends on the pH. The 446 nm band is maximal at pH 7·8 in phenobarbital stimulated musomes and decreases on both lowering and increasing the pH. For metyrapone the apparent spectral dissociation constant K s for the absorbance change at 446 nm was 16 μM in musomes from untreated animals and was decreased to 2·4 μM after phenobarbital pretreatment. In 3-methylcholantrene stimulated musomes the K s value for metyrapone was increased about 25 fold and amounted to 390 μM. The K s value for reduced metyrapone in unstimulated musomes was similar to that for metyrapone. Less pronounced pretreatment effects were, however, observed with this ligand leading to decreased K s values in both PB and MC stimulated musomes. Pyridine and 3-(3-pyridyl)-propanol were only bound to reduced cytochrome P-450 in millimolar concentrations. All tested ligands were able to inhibit musomal drug metabolism. Metyrapone was the most potent inhibitor of drug demethylation exerting 50 per cent inhibition of p -nitroanisole demethylation at 4 μM and of aminopyrine demethylation at 86 μM. Aniline hydroxylation was inhibited by 50 per cent by millimolar concentrations of all inhibitors at aniline concentrations of 4 mM.


Toxicology and Applied Pharmacology | 1977

Ethoxyquin as an inducer and inhibitor of phenobarbital-type cytochrome P-450 in rat liver microsomes.

Regine Kahl; Karl J. Netter

Abstract The effect of ethoxyquin in vivo and in vitro on drug metabolism in rat liver microsomes was studied. In feeding experiments, a threshold dose of induction was found at 0.05% ethoxyquin for 14 days. At 0.5% ethoxyquin, relative liver weight, cytochrome P -450 content, cytochrome b 5 content, ethylmorphine demethylation, and ethoxycoumarin deethylation were increased by a factor of 1.5 to 2. Aryl hydrocarbon hydroxylase activity was, however, not induced but even decreased by 0.5% ethoxyquin in food. Induction of epoxide hydratase was marked, amounting to 400% of control after 0.5% ethoxyquin. The induced enzyme was similar to the phenobarbital-inducible cytochrome P -450 in its CO spectrum, in its affinity for the ligand metyrapone, in the preferential inhibition of monooxygenase activity by metyrapone and not α-naphthoflavone, and in the increase in the phenobarbital-inducible band after gel electrophoresis of microsomal proteins. Mixed pretreatment with ethoxyquin and 3-methylcholanthrene led to formation of cytochrome P -448. However, monooxygenase activities were slightly lower and epoxide hydratase activity was considerably higher than after treatment with 3-methylcholanthrene alone. Ethoxyquin inhibited benzo( a )pyrene hydroxylation and ethoxycoumarin deethylation in vitro . These reactions were less sensitive to ethoxyquin in 3-methylcholanthrene-stimulated microsomes than in phenobarbital-stimulated microsomes, indicating that ethoxyquin does not only preferentially induce but also preferentially inhibits phenobarbital-type cytochrome P -450.


Xenobiotica | 1978

Effect of nitrite on microsomal cytochrome P-450.

Regine Kahl; U. Wulff; K. J. Netter

1. Addition of nitrite to anaerobic rat liver microsomes leads to the appearance of a difference spectrum similar to the spectrum of the ferrous cytochrome P-450-NO complex. A Soret band is found at 444 nm in phenobarbital-stimulated microsomes but at 442 nm in 3-methylcholanthrene-stimulated microsomes. An alpha-band is located at 583 nm in both types of microsome. 2. The initial nitrite-induced difference spectrum is converted into a spectrum lacking a Soret band but with a prominent absorbance minimum at 417 nm. This is more rapid in microsomes from phenobarbital-treated animals where it is completed in 8 min than in microsomes from 3-methylcholanthrene-treated animals. A similar spectrum can be obtained by addition of nitrite to urea-treated microsomes in which cytochrome P-450 has been converted to cytochrome P-420. 3. Azo cleavage of neoprontosil in anaerobic microsomes is markedly inhibited by 1 mM nitrite. In contrast, oxidative drug metabolism is affected only by very high nitrite concentrations around 100 mM. It is concluded that in anaerobic microsomes, NO formed from nitrite complexes with ferrous cytochrome P-450 and thereby inhibits reductive drug metabolism.


Cancer Letters | 1980

Enhancement of epoxide hydratase activity in rat lung, kidney and liver by dietary antioxidants

Regine Kahl

Enhancement of pulmonary epoxide hydratase activity in the rat was obtained by feeding a diet which contained 0.5% ethoxyquin (EQ) or 3,5-di-tert-butyl-4-hydroxytoluene (BHT). The enhancement was less marked (1.6-fold) than in the liver, where a 2-4-fold enhancement of enzyme activity was found after feeding 0.5% antioxidant. A minimal enhancing concentration of 0.1% EQ or BHT in food was established for hepatic epoxide hydratase. In kidney microsomes, elevation of enzyme activity was obtained with 0.5% EQ (1.8-fold), but not with 0.5% BHT. No concomitant increase of cytochrome P-450 content and of aryl hydrocarbon hydroxylase activity was found in the tissues studied.


Biochemical and Biophysical Research Communications | 1984

Different efficiency of various synthetic antioxidants towards NADPH induced chemiluminescence in rat liver microsomes

Andreas Weimann; Alfred G. Hildebrandt; Regine Kahl

The chemiluminigenic probes luminol and lucigenin have been employed to study the production of reactive oxygen species during NADPH oxidation in microsomal preparations. Light emission obtained with lucigenin is 1,000 fold that obtained with luminol. Common food antioxidants differ widely in their ability to cope with microsomal oxygen activation. Propyl gallate proved to be the most potent chemiluminescence inhibitor among five compounds tested while butylated hydroxytoluene was virtually inefficient.


Biochemical Pharmacology | 1974

Effects of synthetic progestagens on drug metabolism in rat liver musomes

Klaus H. Tüttenberg; Bernd Hüthwohl; Regine Kahl; Georg F. Kahl

Evidence is presented that the gestagenic components of hormonal contraceptives norethisterone acetate d-norgestrel and lynestrenol and the progestagen allylestrenol inhibit the oxidative metabolism of p-nitroanisole and aniline in rat liver moicrosomes at concentrations between 5 X 10 less than -5 greater than M and 5 X 10 less than -4 greater than M. Liver microsomes were prepared from male Sprague-Dawley rats. The animals were injected ip with 80 mg of sodium phenobarbital/kg daily for 3 days. They were sacrificed 24 hours after the last injection and 12 hours after food was withdrawn. Livers were perfused in situ with ice-cold saline excised and homogenized. Nuclear fragments and mitochondria were sedimented by centrifugation of the homogenates. Details of technique for the determination of drug metabolizing activity are given. The p-nitroanisole demethylation and aniline hydroxylation in the phenobarbital-stimulated liver micorsomes were inhibited by norethisterone acetate d-norgestrel lynestrenol and allylestrenol. Inhibition was dose-dependent up to a steroid concentration of 1 X 10 less than -4 greater than if complete solubility is assumed. The progestagens inhibit drug metabolism when the concentration of substrate and inhibitor are similar. The situation of women taking oral contraceptives is different from the conditions of the in vitro experiments. In therapy the dose does not exceed 5 mg which is not sufficient to inhibit metabolism of drugs given at the same time. Others have reported excretion of unmetabolized drugs in users of oral contraceptives. More clinical research is needed on the effect of hormonal contraceptives on drug elimination.


Naunyn-schmiedebergs Archives of Pharmacology | 1978

Binding of benzo(a)pyrene metabolites to cellular DNA in perfused rat lungs

B. Deckers-Schmelzle; E. Klaus; Regine Kahl; Georg F. Kahl

SummaryThe influence of pretreatment with monooxygenase inducers on total irreversible binding of metabolically activated [3H]-benzo(a)pyrene to cellular DNA and the formation of benzo(a)pyrene metabolite-deoxyribonucleoside adducts after cytochrome P-448 induction was studied in perfused rat lungs. Pretreatment with the cytochrome P-448 inducer β-naphthoflavone increasing binding by a factor of 23. In lungs of induced animals, 0.45 pmoles of benzo(a)pyrene equivalents were bound per mg DNA. Binding to RNA and to protein was also considerably induced by β-naphthoflavone. Phenobarbital treatment did not significantly increase binding to cellular macromolecules of rat lung. Analysis of hydrolyzed DNA of lungs from β-naphthoflavone-treated rats by Sephadex LH 20 chromatography revealed the formation of at least two nucleoside adducts with metabolically activated benzo(a)pyrene one of which is probably due to modification of the DNA with a benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide and the other to modification of DNA with secondary metabolites of benzo(a)pyrene phenols.


Xenobiotica | 1976

Enhancement of Microsomal Aniline and Acetanilide Hydroxylation by Haemoglobin

Hans G. Jonen; Regine Kahl; Georg F. Kahl

1. Haemogloblin and myoglobin enhance rat liver microsomal p-hydroxylation of aniline and acetanilide. Microsomal N-demethylation of ethylmorphine and aminopyrine is not increased by haemoproteins. 2. The enhancement of microsomal p-hydroxylation is maximal at high substrate concentration and high haeme compound concentration. 3. Detergent-purified NADPH-cytochrome c reductase, free flavins and manganese ions considerably increase the haemoglobin-mediated, tissue-free hydroxylation of aniline. Microsomal aniline hydroxylation is not enhanced by haeme, ferric ion or albumin. 4 Catalase and cyanide ions are powerful inhibitors of haemoglobin-mediated aniline hydroxylation both in the presence and absence of tissue. Carbon monoxide inhibits the hydroxylase activity of the tissue-free system to a smaller extent than that of a system containing microsomes plus haemoglobin whereas p-chloromercuribenzoate inhibits only the flavoprotein-dependent hydroxylation of aniline mediated by haemoglobin. 5. Several possibilities of interactions between substrate, microsomes and haeme compounds are proposed.

Collaboration


Dive into the Regine Kahl's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge