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H M Bolt

Publications and source records attributed to H M Bolt.

At least 235 records · Page 13Linked to original sources
PubMed1976

Metabolism of 14 C-vinyl chloride in vitro and in vivo.

Rat liver microsomes metabolise 14 C-vinyl chloride to intermediates which irreversibly bind to the microsomal protein and to soluble proteins and RNA, when these compounds are added to the incubation. A superoxide (O2) generating system comprised of phenazine methosulfate and NADH also converts 14 C-vinyl chloride to metabolites which irreversibly bind to albumin. These data are consistent with the assumption of chloroethylene oxide being the primary reactive metabolite of vinyl chloride. If rats are exposed to 14 C-vinyl chloride, about half of the radioactive metabolites in the liver microsomal fraction is bound irreversibly to microsomal protein, when assessed immediately after exposure. Large amounts of polar, extractable, metabolites are present in the cytosol fraction. The amount of radioactivity in tissues of the rats, irreversibly bound immediately after exposure, comprises 10 - 40% of the total radioactivity in tissues. This percentage rises up to 70% after 48 hrs. Som radioactivity derived from 14 C-vinyl chloride is also incorporated into DNA and RNA of liver. Whereas the peak of incorporation of 14 C into DNA is already reached immediately after exposure to 14 C-vinyl chloride, specific labelling of RNA increases after exposure until its maximum after 24 hours.

Albumins↗
PubMed1976

[Time course of thioacetamide-induced changes in estrogen metabolism in the rat liver].

Rats have been treated for 6 weeks with thioacetamide (0.1% in drinking water). The biochemical changes in liver microsomal metabolism of estradiol which are similar to those observed in human liver cirrhosis become already apparent after one week of treatment. These are diminishment of hepatic microsomal cytochromes P-450 and b5, comparable decrease of 2-hydroxylation and increase of formation of estrone from estradiol. The alterations of estrogen metabolism are reversible within two weeks after ending thioacetamide treatment. These data correspond to the already well established histological response of rat liver to thioacetamide, and its reversibility.

Acetamides↗
PubMed1976

[Effect of 2-hydroxyestradiol-17beta on NADPH-dependent electron transfer in rat liver microsomes in vitro (author's transl)].

If rat liver microsomes are incubated with NADPH and 2-hydroxyestradiol-17beta in vitro, the following is observed: 1. Inhibition of lipid peroxidation, 2.inhibition of cytochrome P-450 reduction, and 3.inhibition of cytochrome b5 reduction. Beyond this the catechole inhibits lipid peroxidation of liposomes in vitro. These phenomena can be explained by interaction of different states of oxidation of the estrogen with the NADPH-cytochrome reductase and with 0-2 radicals, which leads to terminal "uncoupling" of microsomal electron transport.

Animals↗
PubMed1975

Effect of rifampicin treatment on the metabolism of oestradiol and 17alpha-ethinyloestradiol by human liver microsomes.

Liver biopsies were obtained from four patients treated with rifampicin 600 mg for 6-10 days. Hepatic microsomes were incubated with an NADPH-regenerating system and the substrates [2,4,6,7-3H] oestradiol, [6,7-3H] oestradiol, [2,4,6,7-3H] ethinyloestradiol and [6,7-3H] ethinyloestradiol. The hydroxylation rates of these steroids at the labelled positions of rings A and B were determined by measuring the transformation of tritium into HTO by the microsomal enzymes. Comparison with previously published data showed that treatment with rifampicin caused a fourfold increase in the rate of hydroxylation of oestradiol and ethinyloestradiol at positions C-2/C-4 of ring A and C-6/C-7 of ring B. The acceleration of oestrogen hydroxylation by rifampicin was paralleled by an increase in microsomal cytochrome P-450, and also by microsomal reduction of rifampicin-quinone, a reactive metabolite of rifampicin. The increased aromatic hydroxylation of oestradiol and ethinyloestradiol leads to enhancement of their irreversible binding to microsomal protein. The data provide an explanation for the diminished efficacy of oestrogens in contraceptive formulations given to patients under treatment with rifampicin.

Adult↗
PubMed1975

[The importance of estrogen receptors in the pharmacotherapy of mammary carcinoma (author's transl)].

The physiological effect of estrogens on the estrogen-dependent target organs is mediated by estrogen receptors which are present in the cytoplasm of estrogen-sensitive cells. By determining the estrogen receptors in mammary carcinoma tissue, information may be obtained on the susceptibility of the tumor concerned to hormones. As a novel pharmacological principle, the anti-estrogens are able to blockade the hormonal effect of endogenous estrogens on the tissue of the mammary carcinoma. Possible relationships between prolactin and mammary carcinoma become apparent. From the pharmacologist's point of view, these questions are of particular importance in relation to the possibility of predisposition to mammary carcinoma through treatment with reserpine, which is at present under discussion.

Androgens↗
PubMed1975

[The thioacetamide-poisoned rat as an animal experimental model for endocrinological studies of estrogen metabolism in chronic liver injury)].

Liver microsomes of rats poisoned with thioacetamide show a significant reduction of cytochrome P-450. Consequently, oxidative reactions of drug metabolism and the estrogen 2-hydroxylase are diminished. Enhancement of microsomal transformation of estradiol to estrone and 16alpha-hydroxyestrone is observed after treatment of rats with thioacetamide, due to diminished metabolism of estradiol by the alternative oxidation at C-2. Estriol formation is reduced by thioacetamide pretreatment. These changes in estrogen breakdown closely correlate with those observed in humans suffering from cirrhosis of the liver. It is concluded that the thioacetamide poisoned rat should be an experimental model suitable for studying estrogen metabolism in liver injury.

Acetamides↗