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D C Thompson

Publications and source records attributed to D C Thompson.

At least 91 records · Page 5Linked to original sources
PubMed1989

The peroxidase-dependent activation of butylated hydroxyanisole and butylated hydroxytoluene (BHT) to reactive intermediates. Formation of BHT-quinone methide via a chemical-chemical interaction.

The food antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are shown to be metabolized to covalent binding intermediates and various other metabolites by prostaglandin H synthase and horseradish peroxidase. BHA was extensively metabolized by horseradish peroxidase (80% conversion of parent BHA into metabolites) resulting in the formation of three dimeric products. Only two of these dimers were observed in prostaglandin H synthase-catalyzed reactions. In contrast to BHA, BHT proved to be a relatively poor substrate for prostaglandin synthase and horseradish peroxidase, resulting in the formation of a small amount of polar and aqueous metabolites (23% conversion of parent BHT into metabolites). With arachidonic acid as the substrate, prostaglandin H synthase catalyzed the covalent binding of [14C]BHA and [14C]BHT to microsomal protein which was significantly inhibited by indomethacin and glutathione. The covalent binding of BHA and its metabolism to dimeric products were also inhibited by BHT. In contrast, the addition of BHA enhanced the covalent binding of BHT by 400%. Moreover, in the presence of BHA, the formation of the polar and aqueous metabolites of BHT was increased and two additional metabolites, BHT-quinone methide and stilbenequinone, were detected. The increased peroxidase-dependent oxidation of BHT in the presence of BHA is proposed to occur via the direct chemical interaction of BHA phenoxyl radical with BHT or BHT phenoxyl radical. These results suggest a potential role for phenoxyl radicals in the activation of xenobiotic chemicals to toxic metabolites.

Butylated Hydroxyanisole↗
PubMed1989

Enhancement of the peroxidase-mediated oxidation of butylated hydroxytoluene to a quinone methide by phenolic and amine compounds.

We have recently demonstrated that butylated hydroxyanisole (BHA) markedly stimulates the peroxidase-dependent oxidation of butylated hydroxytoluene (BHT) to the potentially toxic BHT-quinone methide. Using both horseradish peroxidase and prostaglandin H synthase we now report the ability of a wide variety of compounds to stimulate peroxidase-dependent activation of BHT. These compounds include several phenolic compounds commonly present in pharmacologic preparations or occurring naturally in foods. The ability of a given compound to stimulate BHT oxidation was found to depend on the type of radical it forms upon peroxidase oxidation. Compounds which have been shown to form phenoxy radicals or nitrogen-centered cation radicals were observed to enhance BHT oxidation. Conversely, compounds which are known to form peroxy radicals or semiquinone radicals either inhibited or had no effect on BHT oxidation. Compounds which enhanced BHT oxidation (monitored by covalent binding of [14C]BHT to protein) were also observed to stimulate the formation of BHT-quinone methide and stilbenequinone. This suggested a common mechanism of interaction of these compounds with BHT. The stimulation of BHT covalent binding by BHA was also seen in various human and animal tissues using either arachidonic acid or hydrogen peroxide as substrate. The possible toxicologic implications of the enhancement of peroxidase-catalyzed BHT oxidation to BHT-quinone methide are discussed.

Animals↗
PubMed1988

The effect of epithelium removal on non-adrenergic, non-cholinergic inhibitory responses in the isolated central airways of the cat and guinea pig.

Epithelium removal from the feline or the indomethacin-treated guinea pig trachea had no effect on tissue sensitivity or responsiveness to the contractile actions of pharmacological agonists or electrical field stimulation. In the feline hilar bronchus, epithelium removal had no effect on tissue sensitivity or responsiveness to acetylcholine or electrical field stimulation but increased bronchial sensitivity to serotonin without affecting responsiveness. Non-adrenergic non-cholinergic (NANC) relaxation responses elicited by electrical field stimulation in airway preparations from either species were unaffected by epithelium removal. These results suggest that the epithelium does not modulate contractile responses in the feline trachea but may modulate the actions of specific contractile agonists in the feline hilar bronchus. Further, NANC relaxation responses appear to occur independently of the airway epithelium.

Acetylcholine↗
PubMed1988

Enhancement of butylated hydroxytoluene-induced mouse lung damage by butylated hydroxyanisole.

The phenolic antioxidant butylated hydroxytoluene (BHT) is known to produce a dose-dependent increase in mouse lung weight which is characterized by the necrosis of pulmonary type I and endothelial cells. We studied the ability of butylated hydroxyanisole (BHA) to modify BHT-induced changes in lung weight in male CD-1 mice. BHA alone had no effect on lung weight up to a dose of 500 mg/kg (sc). However, when injected 30 minutes prior to sub-threshold doses of BHT (0-250 mg/kg, ip), BHA significantly enhanced lung weight in a dose-dependent manner. The ability of BHA to enhance BHT-induced changes in lung weight was dependent on both the time and the route of administration of BHA relative to BHT. Deuteration of BHT abolished the in vivo toxicity from the combination of BHA and BHT. These results suggest that the toxicity resulting from the combination of BHA and BHT is due to the formation of BHT-quinone methide and that the role of BHA might be either to deplete some protective mechanism in the target pulmonary cells or to enhance the biotransformation of BHT into BHT-quinone methide.

Animals↗
PubMed1988

Studies on the mechanism of enhancement of butylated hydroxytoluene-induced mouse lung toxicity by butylated hydroxyanisole.

The studies described in this report were designed to probe possible mechanisms whereby butylated hydroxyanisole (BHA) is able to enhance butylated hydroxytoluene (BHT)-induced mouse lung toxicity. In experiments with mouse lung slices, BHA enhanced the covalent binding of BHT to protein, indicating that the interaction between BHA and BHT takes place in the lung. Subcutaneous administration of either BHA (250 mg/kg) or diethyl maleate (DEM, 1 ml/kg) to male CD-1 mice produced a similar enhancement of BHT-induced lung toxicity. In contrast to DEM, the administration of BHA (250 or 1500 mg/kg) did not decrease mouse lung glutathione levels, suggesting that the effect of BHA is not due to the depletion of glutathione levels. We previously observed that in the presence of model peroxidases a unique interaction occurs between BHA and BHT, resulting in the increased metabolic activation of BHT. Upon the addition of hydrogen peroxide or various hydroperoxides to mouse lung microsomes, BHA significantly increased the covalent binding of BHT to protein. BHA also stimulated the rate of formation of hydrogen peroxide by 4.7-fold in mouse lung microsomes. Likewise, hydrogen peroxide resulting from the NADPH cytochrome P-450 (c) reductase-catalyzed redox cycling of tert-butylhydroquinone, a microsomal metabolite of BHA, supported the peroxidase-dependent BHA-enhanced formation of BHT-quinone methide. These results suggest that BHA could facilitate the activation of BHT in the lung as a result of both the increased formation of hydrogen peroxide and the subsequent peroxidase-dependent formation of BHT-quinone methide from the direct interaction of BHA with BHT.

Animals↗
PubMed1987

Dental erosion secondary to ethanol-induced emesis.

Case reports within the dental literature have attributed dental erosion to many factors. Severe dental erosion from chronic vomiting, induced by ethanol abuse, has not been previously documented. This article reports such a history and reviews appropriate intervention by the dental practitioner.

Adult↗
PubMed1987

Circumcision.

Explore the source record for details and available documents.

Circumcision, Male↗
PubMed1986

Enhancement of epoxide hydrolase activity in hepatic microsomes of mice given heterocyclic compounds.

The effects of dietary administration of equimolar doses (5 mmol/kg body wt per day) of trimethylene oxide, trimethylene sulfide, coumaran, benzofuran, indole, and indole-3-carbinol on the activities of microsomal epoxide hydrolase and several other xenobiotic metabolizing enzymes were measured in the liver of female CD-1 mouse. Every compound, with the exception of indole, caused a significant increase (P less than 0.01) of the styrene oxide epoxide hydrolase activity over controls in hepatic microsomes. These results indicate that the enzyme activity is elevated in vivo by several heterocyclic compounds with strained bond angles to a nucleophilic hetero-atom. In addition, the ability of sulfur-containing trimethylene sulfide and nitrogen-containing indole-3-carbinol to elevate the enzyme activity indicates that the heterocyclic oxygen atom is not an absolute requirement for this effect. Data from the other xenobiotic metabolizing enzymes indicate that trimethylene oxide and trimethylene sulfide enhance the epoxide hydrolase activity rather specifically, while not affecting the activities of the other enzymes measured. While the oxygen-containing coumaran and benzofuran both increased the NADH: quinone reductase activity in hepatic cytosol, the nitrogen-containing indole and indole-3-carbinol did not. This indicated a specific requirement for the oxygen atom in elevating the quinone reductase activity, which was not the case for the elevation of microsomal epoxide hydrolase activity.

Animals↗
PubMed1986

Aerosolized and intravenously administered leukotrienes: effects on the bronchoconstrictor potency of histamine in the guinea-pig.

The effects of leukotrienes C4 and D4 (LTC4 and LTD4), administered intravenously or by aerosol, on the bronchoconstrictor potency of intravenously administered histamine have been investigated in anaesthetized, mechanically ventilated guinea-pigs. LTC4 (2 nM) had no effect on either the EC50 or the maximum contractile response to histamine on the isolated trachea of the guinea-pig. At 10 nM, LTC4 induced a rightward shift in the histamine concentration-response curve without affecting the maximum response. LTD4 (0.05-0.20 nmol kg-1, i.v.) dose-dependently enhanced histamine (9-36 nmol kg-1, i.v.)-induced increases in airways resistance, whereas equibronchoconstrictor doses of LTC4 (0.1-0.4 nmol kg-1, i.v.), failed to enhance histamine-induced increases in airways resistance. Aerosols of LTC4 and LTD4 generated from solutions of 1-16 microM and administered for 30 s, elicited concentration-dependent bronchoconstrictions comprising decreases in dynamic compliance and increases in airways resistance. At 20 min after exposure to these aerosols, the potency of histamine (9-36 nmol kg-1, i.v.) was significantly increased on both airways resistance and dynamic compliance. The potentiation induced by LTC4 (4 microM, 30 s) was maintained up to 60 min after aerosol exposure whereas that induced by LTD4 (4 microM, 30 s) was maintained up to 40 min after aerosol exposure but was not significantly different (P greater than 0.05, unpaired Student's t test) to saline-exposed animals at 60 min. LTC4 as has been previously reported for LTD4, does not enhance the histamine-induced contraction of isolated airways smooth muscle. In contrast to LTD4, intravenously administered LTC4 does not appear to enhance histamine-induced bronchoconstriction. On the other hand, aerosols of either LTC4 or LTD4 potentiate histamine in vivo in a concentration-dependent manner. These data suggest that leukotrienes may contribute to the regulation of airways reactivity to histamine in the guinea-pig.

Aerosols↗
PubMed1985

Analytical diagnostic peritoneal lavage in the diagnosis of intra-abdominal injury.

Diagnostic peritoneal lavage (DPL) was modified to detect dynamic changes occurring in lavage fluid in dogs following liver, spleen, or intestinal injury. In 33 animals lavage fluid was serially sampled over 75 minutes and analyzed for RBC and other variables. The spun sediment was Gram stained. In control groups, either saline or autologous blood was instilled into the peritoneal cavity at a known rate. In these experiments, the composition of lavage fluid did not significantly change over time. Blood infused at a constant rate into the abdominal cavity produced corresponding, continuing increases in the RBC count. In experimental groups, the liver, spleen, or intestine were injured before lavage. Only initial RBC counts greater than 1 million/mm3 or rising RBC counts in serial lavage samples were associated with life-threatening hemorrhage. Gram stains of samples were positive for bacteria in 43% of fasted dogs and in 80% of fed dogs with intestinal perforation.

Albumins↗
PubMed1985

Modulation of substance P-induced bronchoconstriction by lipoxygenase metabolites.

In anaesthetized, mechanically ventilated guinea-pigs, substance P induces a bronchoconstrictor response comprising increases in airway resistance and decreases in dynamic compliance. Eicosatetraynoic acid (ETYA, 20 mg kg-1 i.v.) or BW755c (20 mg kg-1 i.v.) potentiated the substance P-induced bronchoconstriction. Neither indomethacin (1 or 5 mg kg-1 i.v.) nor aspirin (20 mg kg-1 i.v.) significantly altered the potency of substance P on bronchomotor responses. These observations are consistent with the existence of a bronchodilator lipoxygenase metabolite(s).

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1985

Acetylcholine and histamine interact supra-additively on bronchomotor tone in guinea-pigs in vivo: a possible consequence of the relationship between airways resistance and calibre.

Histamine and acetylcholine administered simultaneously to anaesthetized guinea-pigs result in a bronchoconstriction greater than that of the sum of the individual bronchoconstrictor effects of histamine and acetylcholine administered separately, i.e., a supra-additive interaction. In contrast, a supra-additive effect of acetylcholine and histamine on the isolated tracheal strip did not occur. At a pretreatment concentration of acetylcholine of 5 microM, histamine concentration-response curves were shifted rightwards, i.e., a less than additive interaction, suggesting that, at higher concentrations, histamine and acetylcholine do not act as independent agonists on guinea-pig tracheal smooth muscle. There was no supra-additive interaction between histamine and acetylcholine on tracheal segment tension when measured in situ. These observations suggest that there is no direct interaction between histamine and acetylcholine on the airways smooth muscle cell capable of explaining the supra-additive interaction in vivo. Hexamethonium pretreatment did not alter the magnitude of this supra-additive interaction indicating that an indirect interaction involving autonomic control of airways calibre does not contribute to this phenomenon. The selectivity of the supra-additive interaction for changes in airways resistance rather than compliance, together with the negative evidence for either a direct or an indirect pharmacological interaction between histamine and acetylcholine, suggest that the interaction may result from the physical relationship between airways resistance and airways calibre.

Acetylcholine↗