bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose and sulfate conjugation of phenolic compounds by the spiny lobster (panulirus argus)
Authors: Schell John D. , James Margaret O. 
Published: October 2006

AbstractPrevious work has shown that the hepatopancreas of the spiny lobster (Panulirus argus) contains a mixed‐function oxidase system capable of catalyzing the monooxygenation of polycyclic aromatic hydrocarbons to highly toxic products similar to those formed by mammalian tissues. Studies were designed to determine the ability of the spiny lobster to conjugate the phenolic compounds 4‐methylumbelliferone, p‐nitrophenol, β‐naphthol, and 3‐hydroxy‐benzo[a]pyrene with endogenous molecules. The hepatopancreas contained UDP‐glucose (UDPG) dependent glucosyltransferase, while no activity was detected when UDP‐glucuronic acid was used as the cosubstrate. Atypical Michaelis‐Menten kinetics result with varying concentrations of UDPG, indicating that multiple forms of glucosyltransferase may exist in this organ. The activity was localized in the microsomal fraction, exhibited a pH optimum at 8.0–8.5, and a temperature optimum of 30°C. Sulfate conjugation was found only in the cytosolic fraction of the antennal gland and used adenosine 3′‐phosphate 5′‐phosphosulfate (PAPS) as the sulfate donor (Km (apparent) =9.0 ± 4.9 μM). Hepatopancreas cytosol inhibited sulfotransferase activity. The pH optimum of antennal gland sulfotransferase was a function of the substrate and ranged from 5.5 to 7.4. Analysis of spiny lobster urine 24 hr following exposure to 3‐hydroxybenzo[a]pyrene demonstrated the ability of the lobster to form both the sulfate and glucoside conjugate in vivo.
Oxidative desulfuration of chlorpyrifos, chlorpyrifos‐methyl, and leptophos by rat brain and liver
Authors: Chambers Janice E. , Chambers Howard W. 
Published: October 2006

AbstractThe oxidative desulfuration of the three phosphorothionate insecticides—chlorpyrifos, chlorpyrifos‐methyl, and leptophos—was studied in rat brain and liver. Hepatic microsomes demonstrated activities of 4–28 nmol/g/min, with male activity 2‐ to 4‐fold higher than female activity. Very low desulfuration activity of all three compounds was observed in both microsomal and crude mitochondrial fractions from brain (3–27 pmol/g/min). There were no sex differences in the brain. Although the liver displayed 140‐ to 2100‐fold greater activity than brain on a wet‐weight basis, the brain desulfuration activities of these three compounds as well as those of some previously reported phosphorothionates generally correlate well with the toxicity and may be important in determining the overall acute toxicity levels of phosphorothionate insecticides.
Induction of peroxisomal enzymes in cultured porcine endothelial cells by the hypolipidemic drug ciprofibrate
Authors: Glauert Howard P. , Hennig Bernhard , Chow Hannah S. 
Published: October 2006

AbstractThe purpose of this study was to determine if the hypolipidemic peroxisome proliferator ciprofibrate, which induces peroxisomes in the liver, can induce peroxisomes in cultured porcine pulmonary endothelial cells. Ciprofibrate was added at three concentrations to cell cultures for a 6‐day period. The induction of peroxisomes in the cells was detected by determining total peroxisomal β‐oxidation and peroxisomal catalase activity. The addition of ciprofibrate was found to increase peroxisomal enzyme activities in a dose‐dependent manner, with the highest activity being reached at 1000 μM ciprofibrate. Ciprofibrate also caused an increased transfer of albumin across endothelial cells cultured on micropore filters. This study shows that peroxisomal enzyme activities can be induced by ciprofibrate in endothelial cells, which may have implications in diseases mediated by vascular injury.
Mirex induces ornithine decarboxylase in female rat liver
Authors: Mitra Ashoke , Richards Ira , Kitchin Kirk , Conolly Rory , Kulkarni Arun P. 
Published: October 2006

AbstractOrnithine decarboxylase, the rate‐limiting enzyme in polyamine synthesis, was significantly induced in female rat liver following oral administration of the pesticide mirex. After dual oral exposure (120 mg /kg of mirex; 21 and 4 hr prior to sacrifice), ornithine decarboxylae activity in rat liver cytosol was 70‐fold higher than control values. A single oral dose of mirex (180 mg /kg) induced hepatic ornithine decarboxylase activity 55‐fold over controls. After a single oral dose of mirex the maximal induction of ODC activity occurred at 36 hr. Mirex is an unusually potent and long‐lasting inducer of rat hepatic ornithine decarboxylase activity.
The effects of ions on the conjugation of xenobiotics by the aralkyl‐coa and arylacetyl‐coa N‐acyltransferases from bovine liver mitochondria
Authors: Kelley Michael , Vessey Donald A. 
Published: October 2006

AbstractThe aralkyl‐CoA:glycine N‐acyltransferase and the arylacetyl‐CoA:amino acid of N‐acyltransferase were purified from bovine liver mitochondria and their response to a variety of ions investigated. The activity of the aralkyl transferase was inhibited by divalent cations and high concentrations of monovalent cations with all substrates investigated. For benzoyl‐coenzyme A (CoA), K+ was a competitive inhibitor, competing for binding at the benzoyl‐CoA binding site. With salicylyl‐CoA, K+ did increase the dissociation constant (KD) for acyl‐CoA but it was not a competitive inhibitor and in addition, K+ increased the Michaelis constant for glycine (Kglym) tenfold. The data suggest that the increase in Kglym is due to bound K+ forcing reorientation of salicylyl‐CoA at the active site so that it impinges on the glycine binding site. Inorganic anions and cations did not affect the extent of product inhibition by hippuric acid with either acyl‐CoA and this was because they affected the binding of acyl‐CoA and hippuric acid to the same extent. Ions did, however, greatly reduce the extent of product inhibition by CoA. This is critical because under approximate in vivo conditions (2.5 mM CoA), the salt‐free enzyme would be almost completely inhibited by CoA. The arylacetyl transferase was activated by inorganic ions when assayed at saturating substrate concentrations. However, at physiologic concentrations of glycine certain salts were modestly inhibitory. The inhibitory effect of KCl was characterized by a large decrease in the affinity of the enzyme for phenylacetyl‐CoA, suggesting that the arylacetyl‐CoA region of the active site contained an inhibitory ion binding site. At low (physiologic) concentrations of substrate, the arylacetyl transferase was extensively inhibited by CoA and this inhibition was greatly reduced by ions. The 3′‐phosphate group on CoA was found to be important for binding to the salt‐free enzyme but in the presence of ions its importance was diminished. In the absence of inorganic ions the affinity of the enzyme for phenylacetyl‐CoA and naphthylacetyl‐CoA was so high that it could not be measured. In the presence of KCl the KD values for phenylacetyl‐CoA and naphthylacetyl‐CoA were similar, but the Km for glycine was extremely high for 1‐naphthylacetyl‐CoA conjugation, which accounts for its slow rate of metabolism. Conjugation with glutamine had a high Michaelis constant for glutamine (KGlum) and a low maximum velocity (Vmax) which accounts for the absence of glutamine conjugation in vivo.
Oxidatively stressed lymphocytes remain in Go/Gla on mitogenic stimulation
Authors: Duncan David D. , Lawrence David A. 
Published: October 2006

AbstractThiol modifiers and oxidants inhibit lymphocyte activation. To investigate which of the many cell functions sensitive to oxidation are critical in this inhibition, mouse splenic lymphocytes were treated with oxidants prior to exposure to mitogen, and progression into the cell cycle was assayed. Different treatments were used to chemically dissect different potential targets within the cell: copper phenanthroline (CuP), to oxidize surface sulfhydryls; N‐ethyl maleimide (NEM), to alkylate extra‐ and intracellular thiols; and hydrogen peroxide, which generates the highly reactive hydroxyl radical within the cell. Progression into the cell cycle was assayed with acridine orange (AO) and assays of interleukin‐2 (IL‐2) production and IL‐2 receptor (IL‐2R) expression. The contribution of ADP‐ribosylation to inhibition of mitogenesis was assessed using 3‐aminobenzamide (3AB) to inhibit adenosine 5′‐diphosphate (ADP)‐ribose transferases. The results indicate that the CuP and NEM treatments both produce two independent inhibitory effects, that is, a failure in the production of and response to IL‐2. Cells treated with these compounds were able to progress only through G1a upon mitogenic stimulation. H2O2 had more complex effects. Both ADP‐ribosylation and modulations of cytosolic Ca2+ were involved in the inhibitory effects. With lower inhibitory doses of H2O2, lymphocytes were completely unresponsive to mitogen and failed to exit Go upon mitogenic stimulation. If intra‐ and extracellular Ca2+ were buffered before treatment with H2O2, higher concentrations were required, and under these conditions cells were able to enter G1a but could not progress into G1b. Under neither of these conditions could cells produce IL‐2 or express IL‐2R.
Alteration in de novo pyrimidine biosynthesis during uridine reversal of pyrazofurin‐inhibited dna synthesis
Authors: Ringer David P. , Howell Boyd A. , Etheredge Janet L. 
Published: October 2006

AbstractPyrazofurin, a pyrimidine nucleoside analogue with antineoplastic activity, inhibits cell proliferation and DNA synthesis in cells by inhibiting uridine 5′‐phosphate (UMP) synthase. It has been previously shown in concanavalin A (con A)‐stimulated guinea pig lymphocytes (23) that pyrazofurininhibited DNA synthesis could be selectively reversed by exogenous uridine (Urd). In this report, we have examined possible mechanisms for the Urd reversal with experiments that determine the ability of exogenous Urd to (a) interfere with either the intracellular transport of pyrazofurin, or the conversion of pyrazofurin to its intracellularly active form, pyrazofurin‐5′‐phosphate; (b) reverse the pyrazofurin block of [14C]orotic acid incorporation into DNA; and (c) alter the pattern of exogenous [3H]Urd incorporation into DNA‐thymine (DNA‐Thy) and DNA‐cytosine (DNA‐Cyt) during pyrazofurin inhibition of pyrimidine de novo biosynthesis. The results of these experiments showed that Urd reversal does not occur through altered pyrazofurin transport or intracellular conversion to pyrazofurin‐5′‐phosphate, nor does it alter the distribution of [3H]Urd in DNA‐Thy and DNA‐Cyt. Instead, these findings indicate that the primary mechanism for exogenous Urd reversal of pyrazofurin inhibition of DNA synthesis involves the reversal of pyrazofurin inhibition of UMP synthase, thus restoring orotic acid incorporation into lymphocyte DNA through the pyrimidine de novo pathway.
Fetotoxic alterations in the normal ontogenies of rat microsomal and lysosomal enzymes
Authors: Harris Craig , Thomas David E. , Carter Melvin W. , Bradshaw William S. 
Published: October 2006

AbstractThe activity patterns during development for acid phosphatase (Ac‐P), alkaline phosphatase (A1‐P), ß‐glucuronidase (ßG), and UDP‐glucuronyltransferase (UDPGT) have been determined in various tissues of the rat for corn oil and distilled water controls as well as in animals prenatally exposed to four fetotoxic chemicals. Postnatal assays were performed on both sexes separately. In control animals, tissue‐specific differences between male and female activity levels were found for UDPGT. In the liver of mature offspring, enzyme activity was greater in males than in females. Although no sex difference was observed in the intestine, the kidneys of females exhibited higher values than those of males. An original computer‐assisted methodology is presented, designed (a) to permit a mathematical description for the complex curves exhibited by these ontogeny profiles, and (b) to assess the statistical significance of chemical‐induced alterations in these complex developmental patterns, specifically, to target sensitive periods and subtle changes near the fetotoxic threshold. Oral administration (days 6–18 of gestation) of 3,3′,4,4′‐tetrachlorobiphenyl (4CB) to pregnant females resulted in an induction of liver UDPGT activity in offspring postnatally, and some alterations in the perinatal pattern of ßG in the same tissue. This treatment also produced differences in the intestinal patterns of Ac‐P and male UDPGT. No significant changes were observed in offspring exposed to diethylstilbestrol (DES). Treatment with zeranol (ZN) caused reductions in activity over the entire postnatal period for ßG in liver, brain, intestine, and kidney, for Al‐P in brain, and for Ac‐P in the intestine. Cadmium‐treated dams gave birth to offspring that exhibited slightly altered ontogenies only in intestine for UDPGT and AcP. The alterations in these developmental profiles indicate periods of increased sensitivity, and may be useful in directing more specific studies into the fetotoxic mechanisms of these compounds.
Pentachlorobutadienyl‐l‐cysteine (PCBC) toxicity: The importance of mitochondrial dysfunction
Authors: Groves Carlotta E. , Schnellmann Rick G. , Sokol Paul P. , Steffens Thomas G. , Lock Edward A. 
Published: October 2006

AbstractThe relationship between the covalent binding, uptake, and toxicity produced by pentachlorobutadienyl‐L‐cysteine (PCBC) was examined in rabbit renal proximal tubules (RPT), renal basolateral membrane vesicles, and isolated renal cortical mitochondria. Renal proximal tubules rapidly metabolized PCBC to a reactive intermediate that bound to tubular protein. Approximately 70–90% of PCBC found in the cell at any given time was bound to protein. PCBC initially uncoupled oxidative phosphorylation, followed by a 45% reduction of state 3 respiration and a 90% decrease in cellular adenosine triphosphate (ATP) levels. These events preceded cell death. Isolated mitochondria also metabolized PCBC to a reactive intermediate that bound to mitochondrial protein and initiated mitochondrial toxicity. These results show that. PCBC‐induced mitochondrial dysfunction occurred as a result of mitochondrial bioactivation and that the mitochondrion is the critical subcellular target in PCBC toxicity. Aminooxyacetic acid (AOAA), an inhibitor of cysteine conjugate β‐lyase, reduced the covalent binding of PCBC‐equivalents to tubular protein by approximately 90% and decreased but did not prevent the toxic effects produced by PCBC on RPT respiration and cellular ATP levels. AOAA delayed but had no effect on the overall extent of cell death produced by PCBC. The protective effect of AOAA was independent of any effects on PCBC uptake. These results show that AOAA decreased but did not prevent the metabolism of PCBC by cysteine conjugate β‐lyase. The partial inhibition of PCBC metabolism, and hence, PCBC‐induced cell death by AOAA, may be related to limited concentrations of AOAA within the tubule cell or mitochondria.
Lead influences translational or posttranslational regulation of ia expression and increases invariant chain expression in mouse B cells
Authors: McCabe Michael J. , Dias James A. , Lawrence David A. 
Published: October 2006

AbstractThe molecular mechanisms governing the increased cell surface expression of major histocompatibility complex (MHC) class II molecules (Ia) on lead‐treated mouse B cells was investigated. Lead has been shown to directly cause a selective, two‐fold increase in the B cell's surface density of both products of the I region of the mouse MHC, I‐A and I‐E. In the present study, Western blot analysis showed that Pb increases the total cellular pool of I‐A β‐chain by twofold. The increase in cellular I‐A was not found to be due to increased messenger RNA (mRNA) for either the α‐ or the β‐chain of I‐A. Biosynthetic labeling studies showed that Pb increases the translation or the stability of the Ia‐associated invariant chain (Ii or γ) and possibly the β‐chain of Ia. Collectively these results suggest that Pb increases the B cell's surface Ia by influencing translational or posttranslational regulation of Ia and/or Ia‐associated chains.
Reactivity of Hg(II) with superoxide: Evidence for the catalytic dismutation of superoxide by HG(II)
Authors: Miller Dennis M. , Lund Bert‐Ove , Woods James S. 
Published: October 2006

AbstractMercuric ion, a well‐known nephrotoxin, promotes oxidative tissue damage to kidney cells. One principal toxic action of Hg(II) is the disruption of mitochondrial functions, although the exact significance of this effect with regard to Hg(II) toxicity is poorly understood. In studies of the effects of Hg(II) on superoxide (O) and hydrogen peroxide (H2O2) production by rat kidney mitochondria, Hg(II) (1–6 μM), in the presence of antimycin A, caused a concentration‐dependent increase (up to fivefold) in mitochondrial H2O2 production but an apparent decrease in mitochondrial O production. Hg(II) also inhibited O‐dependent cytochrome c reduction (IC50 ≈︁2–3 μM) when O was produced from xanthine oxidase. In contrast, Hg(I) did not react with O in either system, suggesting little involvement of Hg(I) in the apparent dismutation of O by Hg(II). Hg(II) also inhibited the reactions of KO2 (i.e., O) with hemin or horseradish peroxidase dissolved in dimethyl sulfoxide (DMSO). Finally, a combination of Hg(II) and KO2 in DMSO resulted in a stable UV absorbance spectrum [currently assigned Hg(II)‐peroxide] distinct from either Hg(II) or KO2. These results suggest that Hg(II), despite possessing little redox activity, enhances the rate of O dismutation, leading to increased production of H2O2 by renal mitochondria. This property of Hg(II) may contribute to the oxidative tissue‐damaging properties of mercury compounds.
Whether cytochrome p450 induction accompanies glucuronosyl and glutathione transferase induction by isomers of dipyridyl appears unrelated to dose and iron chelation properties
Authors: Franklin Michael R. 
Published: October 2006

AbstractAdministration of 4, 4′dipyridyl to rats induces the activities of xenobiotic transferases (phase II drug metabolizing enzymes), UDP‐glucuronosyl‐tranferase and glutathione‐S‐transferase, and also the concentration and activity of cytochrome P450 (a phase I drug metabolizing enzyme). 2, 2′Dipyridyl, an isomer possessing iron chelation properties, only induces the phase II enzymes. Although the magnitude of the phase II induction by 2, 2′dipyridyl increases with increasing dosages, the selective induction of only phase II activities remains inviolate. Co‐administration of 2, 2′dipyridyl does not prevent 4, 4′dipyridyl from inducing cytochrome P450, suggesting that the iron chelation property is not the factor that precludes 2, 2′dipyridyl from coordinately inducing cytochrome P450 with the transferases.
Effects of diphenyl ether herbicides on porphyrin accumulation by cultured hepatocytes
Authors: Jacobs Judith M. , Sinclair Peter R. , Gorman Nadia , Jacobs Nicholas J. , Sinclair Jacqueline F. , Bement William J. , Walton Heidi 
Published: October 2006

AbstractSeveral diphenyl ether herbicides, such as acifluorfen methyl, have been previously shown to cause large accumulations of the heme and chlorophyll precursor, protoporphyrin, in plants. Lightinduced herbicidal damage is mediated by the photoactive porphyrin. Here we investigate whether diphenyl ether herbicides can affect porphyrin synthesis in rat and chick hepatocytes. In rat hepatocyte cultures, protoporphyrin, as well as coproporphyrin, accumulated after treatment with acifluorfen or acifluorfen methyl. Combination of acifluorfen methyl with an esterase inhibitor to prevent the conversion of acifluorfen methyl to acifluorfen resulted in a greater accumulation of porphyrins than caused by acifluorfen methyl or acifluorfen alone. In vitro enzyme studies of hepatic mitochondria isolated from rat and chick embryos demonstrated that protopor‐phyrinogen oxidase, the penultimate enzyme of heme biosynthesis, was inhibited by low concentrations of acifluorfen, nitrofen, or acifluorfen methyl with the latter being the most potent inhibitor. These findings indicate that diphenyl ether treatment can cause protoporphyrin accumulation in rat hepatocyte cultures and suggest that this accumulation was associated with the inhibition of protoporphyrinogen oxidase. In cultured chick embryo hepatocytes, treatment with acifluorfen methyl plus an esterase inhibitor caused massive accumulation of uroporphyrin rather than protoporphyrin or coproporphyrin. Specific isozymes of cytochrome P450 were also induced in chick embryo hepatocytes. These effects were not observed in the absence of an esterase inhibitor. These results suggest that diphenyl ether herbicides can cause uroporphyrin accumulation similar to that induced by other cytochrome P450‐inducing chemicals such as polyhalogenated aromatic hydrocarbons in the chick hepatocyte system.
Stimulation of the active transport of serotonin into mouse platelets by the sulfhydryl oxidizing agent diamide
Authors: Bosin Talmage R. , Kasper Gregory C. 
Published: October 2006

AbstractThe purpose of this study was to determine the effects of diamide, a reversible sulfhydryl oxidizing agent, on the transport of serotonin (5‐HT) by mouse platelets. Diamide produced a concentration‐dependent (10–200 μM) stimulation of 5‐HT transport that was rapid and sustained over 0–10 minutes of incubation. When platelets were incubated with diamide (10–200 μM) in the presence of glucose, the content of reduced glutathione was significantly decreased only at a final concentration of 200 μM, while washed platelets incubated with diamide (10–200 μM), in the absence of glucose, had a significant concentration‐dependent decrease in their content of reduced glutathione. Fluoxetine, an inhibitor of the platelet 5‐HT transporter, blocked diamide‐induced stimulation of 5‐HT transport. The kinetics of 5‐HT transport showed that diamide caused a marked increase in the maximal rate of transport (Vmax control = 28.4 ± 1.4 vs. Vmax diamide = 60.9 ± 4.1 pM/108 platelets/4 min) but did not significantly alter the Km values. Ouabain, an inhibitor of platelet Na+‐K+ ATPase, blocked the stimulation by diamide in a concentration‐dependent manner. Dithiothreitol, a disulfide reducing agent, was able to partially reverse the stimulation of platelet 5‐HT transport caused by diamide. This study has shown that diamide can stimulate the active transport of 5‐HT by mouse platelets and suggests a possible role for free sulfhydryl groups in the regulation of this process.
Strand scission in DNA by Gossypol and Cu(II): Role of Cu(I) and oxygen‐free radicals
Authors: Zaidi Rana , Hadi S. M. 
Published: October 2006

AbstractGossypol, a polyphenolic binaphthyl dialdehyde found in cotton seeds, is a dietary mutagen and a potential male contraceptive. In the presence of Cu(II), gossypol caused breakage of supercoiled plasmid pBR322 DNA. The products were relaxed circles or a mixture of these and linear molecules. Other metal ions tested [Ni(II), Co(II), Mn(II), and Fe(II)] were ineffective or less effective in the DNA breakage reaction. In the case of gossypol‐Cu(II) mediated cleavage, (Cu(I) was shown to be an essential intermediate by using the Cud) sequestering reagent bathocuproine. By using job plots, it was established that in the absence of DNA, eight Cu(II) ions can be reduced by one gossypol molecule. The involvement of active oxygen species, such as singlet oxygen and H2O2, was established by the inhibition of DNA breakage by catalase and by sodium azide. It was further shown that gossypol is capable of directly producing H2O2.