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Biomedical subjects

B B Davis

Publications and source records attributed to B B Davis.

At least 145 records · Page 8Linked to original sources
PubMed1980

Metabolism of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide by prostaglandin endoperoxide synthetase.

Cooxidative metabolism of the urinary bladder carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) was examined using solubilized and particulate microsomal preparations from the rabbit renal inner medulla and the ram seminal vesicle. Metabolism was measured by the rate of decrease in absorbance at 400 nm. In these soluble and particulate preparations, FANFT metabolism was observed only in the presence of specific fatty acids. These fatty acids are substrates for prostaglandin endoperoxide synthetase. Structurally dissimilar inhibitors of prostaglandin endoperoxide synthetase such as indomethacin, aspirin, 5,8,11,14-eicosatetraynoic acid, ethoxyquin, and meclofenamic acid specifically inhibited FANFT metabolism. Other inhibitor and substrate specificity studies suggest that FANFT was not metabolized by nitroreductase, xanthine oxidase, lipoxygenase, lipid peroxidation, or mixed-function oxidases. In addition, the lack of detectable 2-amino-4-(5-nitro-2-furyl)thiazole formation suggests that arylformamidase was not participating in FANFT metabolism measured in these experiments. The data indicate that prostaglandin endoperoxide synthetase can mediate FANFT metabolism by a cooxidative process.

Animals↗
PubMed1980

Benzidine binding to nucleic acids mediated by the peroxidative activity of prostaglandin endoperoxide synthetase.

The cooxidative metabolism of the urinary bladder carcinogen benzidine was examined using renal inner medullary microsomes. The products of [14C]benzidine metabolism were recovered in the aqueous but not in the organic soluble fraction of reacting mixtures. The reactive metabolites formed during cooxidative metabolism of benzidine bound to DNA and transfer RNA. Cooxidative metabolism of benzidine and subsequent binding to nucleic acids was dependent upon specific fatty acid substrates and was blocked by inhibitors of prostaglandin endoperoxide synthetase. The ratio of the rates of benzidine product formation was approximately 10:3:1 (trichloroacetic acid precipitable:non-trichloroacetic acid precipitable:transfer RNA bound) over a wide range of arachidonic acid concentrations. Cumene hydroperoxide also initiated cooxidative metabolism of benzidine but was less effective than was arachidonic acid. In contrast to arachidonic acid, cumene hydroperoxide-mediated metabolism of benzidine and fuaiacol peroxidase activity was not blocked by indomethacin. Using electron paramagnetic resonance, radicals were detected after addition of arachidonic acid or cumene hydroperoxide to the microsomal preparation. Radical production was completely quenched by addition of benzidine or guaiacol. These results demonstrate that the peroxidative activity of renal medullary prostaglandin endoperoxide synthetase mediates benzidine metabolism and subsequent binding to nucleic acids.

Animals↗
PubMed1980

Co-oxidative metabolism of 2-amino-4-(5-nitro-2-furyl)-thiazole by prostaglandin hydroperoxidase.

Co-oxidative metabolism of ANFT by either the fatty acid cyclo-oxygenase or hydroperoxidase activities of prostaglandin endoperoxide synthetase was examined by using solubilized and particulate microsomes prepared from rabbit renal inner medulla and ram seminal vesicles. The rate of metabolism was measured by the decrease in absorbance at 385 nm. In both soluble and particulate preparations, ANFT metabolism was dependent upon specific fatty acid substrates and prevented by specific inhibitors of prostaglandin endoperoxide synthetase. Other inhibitor and substrate specificity studies suggest that ANFT was not metabolized by xanthine oxidase, lipoxygenase, lipid peroxidation, or mixed-function oxidases. Under incubation conditions which demonstrated co-oxidation of ANFT, a metabolite (peak I) was observed by high-pressure liquid chromatography. In the presence of indomethacin, peak I was not present, and only authentic ANFT was observed. Co-oxidation of ANFT was also observed with cumene hydroperoxide. Cumene hydroperoxide-mediated co-oxidation was not prevented by indomethacin or SKF-525A but was blocked by the antioxidants butylated hydroxytoluene, ethoxyquin, and vitamin E. The data indicate that ANFT is metabolized by a co-oxidative process involving the prostaglandin hydroperoxidase activity of prostaglandin endoperoxide synthetase.

Animals↗
PubMed1980

Metabolism of benzidine by a prostaglandin-mediated process in renal inner medullary slices.

Renal inner medullary slices were used to investigate the metabolism and subsequent binding to tissue of [14C]-benzidine metabolite(s) and the effect of benzidine on radioimmunoassayable prostaglandin (PG) E2 synthesis. Benzidine elicited a dose-dependent, reversible inhibition of PGE2 synthesis. By contrast, aspirin inhibition of PGE2 synthesis was not reversible. Binding of [14C]-benzidine metabolite(s) to medullary tissue was observed. This binding was increased by arachidonic acid. Arachidonic acid-mediated binding was prevented by inhibitors of prostaglandin endoperoxide synthetase. Metyrapone and SKF-525A, inhibitors of mixed function oxidase activity, did not inhibit binding of benzidine metabolite(s). Fatty acids which are not substrates for prostaglandin endoperoxide synthetase did not increase binding. These results are consistent with previous studies demonstrating inner medullary microsomal cooxidative metabolism of benzidine by prostaglandin endoperoxide synthetase and document the cooxidative process proceeds in an intact cell preparation, the tissue slice. The renal inner medulla is a potential site for the cooxidative metabolism of drugs and xenobiotics which require activation before eliciting their toxic effects on the urinary tract.

Animals↗
PubMed1979

Cooxygenation by prostaglandin cyclooxygenase from rabbit inner medulla.

The renal inner medulla may be exposed to high concentrations of organic compounds which are excreted into the urine. This report examines the capacity of the inner medulla to metabolize organic compounds both in vitro and in vivo. The compounds used were 1,3-diphenylisobenzofuran (DPBF), luminol, and benzidine. The inner medulla was shown to possess the capacity to oxidize each of these compounds. Microsomal oxygenation did not require NADPH. Cytochorome P-450 inhibitors carbon monoxide and metyrapone did not reduce DPBF metabolism. Lipoxygenase activity was not detected in inner medullary microsomes. Oxygenation of DPBF was demonstrated in inner medullary slices and was inhibited by indomethacin. The product of DPBF metabolism in renal slices and microsomes was identified as O-dibenzoylbenzene. In vivo experiments demonstrated benzidine metabolism, which was blocked by meclofenamic acid. On the basis of substrate specificity and inhibitor studies, it was concluded that oxygenation of DPBF, luminol, and benzidine was mediated by prostaglandin cyclooxygenase. These results are compatible with cooxygenation being a mechanism of inner medullary drug metabolism.

Animals↗
PubMed1979

Effect of age on intestinal calcium absorption and adaptation to dietary calcium.

To study the reported decline in intestinal calcium absorption with age, calcium active transport, immunoreactive calcium protein (CaBP) content, and alkaline phosphatase activity were measured in the intestine of two strains of rats aged 3-wk--20 mo. Calcium active transport, as measured by everted gut sacs from Sprague-Dawley rats, was greatest at 3 wk, but it declined rapidly with no active transport demonstrable at 3 mo or thereafter. CaBP content closely paralleled the decline in active transport, but alkaline phosphatase activity increased as active transport decreased. Intestinal adaptation to dietary calcium was studied by feeding high- and low-calcium diets to Fischer 344 rats aged 1.5--12 mo. In 1.5-mo-old rats fed a low-calcium diet, there was an increase in calcium active transport, CaBP content, and alkaline phosphatase activity relative to animals fed a high-calcium diet. However, the magnitude of this intestinal adaptation decreased with age until there was only marginal adaptation by 12 mo. The observed changes in calcium active transport with age and diet may be explained by the parallel changes in the vitamin D-dependent CaBP content of the intestine.

Aging↗