bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perturbations in polyamines and related enzymes following chlordecone‐potentiated bromotrichloromethane hepatotoxicity
Authors: Rao Shrinivas B. , Young Robert A. , Mehendale Harihara M. 
Published: October 2006

AbstractThe mechanism by which chlordecone (CD) amplifies the hepatotoxicity of halomethanes such as CCl4, CHCl3, and BrCCl3 has been a subject of intense study. Recent work has shown that suppression of hepatocellular regeneration leads to accelerated progression of liver injury leading to complete hepatic failure due to an unusual interaction between individually nontoxic low‐dose combination of CD and CCl4. Since polyamines are involved in cell division, their levels reflect the extent to which there is suppression of hepatocellular regeneration during CD and CCl4 interaction. The present studies were designed to investigate the polyamine levels and associated enzymes in livers of rats treated with BrCCl3 alone or CD and BrCCl3 low‐dose combination in order to confirm whether the sequence of events of hepatotoxicity is similar to that seen in CCl4 toxicity or that seen during CD and CCl4 interaction. The extent of liver toxicity in rats fed 10 ppm chlordecone (CD) for 15 days prior to the injection of a single low dose of BrCCl3 (15 μL/kg body weight) or after exposure to a high dose of BrCCl3 (80 μL/kg body weight) without CD pretreatment, was similar 6 and 24 hr later as assessed by plasma transaminase levels. There was also an increase in transaminase levels, in rats exposed to a single low dose of BrCCl3 alone (15 μL/kg body weight) but this increase was far below the high‐dose exposure alone or the combination treatment. Hepatic levels of ornithine decarboxylase, S‐adeno‐sylmethionine decarboxylase, N1‐acetylputrescine, N1‐acetylspermidine, putrescine, spermidine, and spermine at the end of 24 hr increased after exposure to a low dose of BrCCl3 alone as compared to exposure to a high dose alone or the low‐dose combination of CD and BrCCl3. Liver spermidine N1‐acetyltrans‐ferase was elevated at 2, 6, and 24 hr after exposure to a high dose of BrCCl3 alone as compared to treatment with a low‐dose combination of CD and BrCCl3 suggesting decreased synthesis of this enzyme, in spite of a greater need as seen from liver transaminase levels. In general, it was observed that there is significant elevation in some polyamines and related enzymes during toxicity of a low dose of BrCCl3 which seemed to stabilize within 24 hr. This was not observed with the other two groups of rats exposed either to BrCCl3 high dose alone or the low‐dose combination of CD and BrCCl3. Results indicate that CD and BrCCl3 low‐dose combination treatment causes increased liver toxicity resulting in compromised polyamine metabolism which is coincidental with suppressed hepatocellular regeneration leading to accelerated progressive phase of liver injury culminating in complete hepatic failure. These findings point to the possibility that the mechanism of potenti‐ation of BrCCl3 hepatotoxicity by CD is similar to that seen for CD and CCl4 interaction.
Neonatal modulation of adult rat hepatic microsomal benzo[a]pyrene hydroxylase activities by aroclor 1254 or phenobarbital
Authors: Haake‐McMillan J. M. , Safe S. H. 
Published: October 2006

AbstractThe constitutive and Aroclor 1254‐in‐duced activities of hepatic microsomal benzo[a]‐pyrene hydroxylases in male and female rats were determined in animals from ages 11 to 120 days. In 11‐day‐old noninduced male rats, benzo[a]pyrenediones and 9‐hydroxybenzo[a]pyrene were the major microsomal metabolites; in 21‐day‐old males benzo[a]pyrene‐diones and benzo[a]pyrene‐9,10‐dihydrodiol were predominant. In 60‐ and 120‐day‐old animals 3‐hydroxybenzo[a]pyrene was the major microsomal metabolite. A similar trend was observed for the development of benzo[a]pyrene hydroxylase activities in female rats. With the exception of 4,5‐di‐hydrodiol formation, the highest induction of individual and total benzo[a]pyrene hydroxylase activities by Aroclor 1254 was observed in the 21‐day‐old immature male rats, in which there was a 330‐ and 4.5‐fold increase in the formation of 3‐hydroxybenzo[a]pyrene and quinone metabolites, respectively. The induction of benzo[a]pyrene total metabolite formation by Aroclor 1254 in female rats from 11 to 120 days of age was relatively constant (i.e., 13.3‐ to 10.1‐fold induction); however, the relative induction of the individual benzo[a]pyrene hydroxylases was highly variable. In a second set of experiments, male and female rats were neonatally exposed to phenobarbital (600 μmol/kg) or Aroclor 1254 (100 μmol/kg), and the effects of these xenobiotics on neonatal imprinting of hepatic microsomal benzo[a]pyrene hydroxylase activities were determined in the 120‐day‐old animals. Neonatal exposure to phenobarbital resulted in a decrease in the Aroclor 1254‐induced rates of formation of dihydrodiol and quinone benzo[a]pyrene metabolites in male rat microsomes, an increase in the rates formation of the 9,10‐ and 7,8‐dihydrodiols in Aroclor 1254‐induced female rat microsomes, and a decrease in the constitutive and Aroclor 1254‐induced 3‐ and 9‐hydroxylase activities in hepatic microsomes from either sex. Neonatal exposure to Aroclor 1254 (100 μmol/kg) resulted in significantly lower Aroclor 1254‐induced rates of formation of the 9,10‐, 4,5‐ and 7,8‐dihydrodiol, quinone, and 9‐hydroxybenzo[a]pyrene metabolites in 120‐day‐old male rat microsomes and significantly decreased rates of formation of the 4,5‐dihydrodiol and quinone benzo[a]pyrene metabolites in Aroclor 1254‐induced female rat hepatic microsomes. Only minor differences were observed in the constitutive benzo[a]pyrene hydroxylase activities in microsomes from male or female rats neonatally treated with either phenobarbital or Aroclor 1254. These results demonstrate that neonatal exposure to phenobarbital or Aroclor 1254 can alter the adult metabolism of xenobiotics such as benzo[a]pyrene.
Linoleic acid‐induced endothelial cell injury: Role of membrane‐bound enzyme activities and lipid oxidation
Authors: Ramasamy Santhini , Boissonneault Gilbert A. , Decker Eric A. , Hennig Bernhard 
Published: October 2006

AbstractHigh plasma levels of linoleic acid (18:2) may injure endothelial cells, resulting in decreased barrier function of the vascular endothelium. The effects of linoleic acid on endothelial barrier function (transendothelial movement of albumin), membrane‐bound enzyme activities, and possible autooxidation of linoleic acid under experimental conditions were studied. The exposure of endothelial monolayers to 18:2 for 24 hr at 60, 90, and 120 μM. fatty acid concentrations caused a significant increase in transendothelial movement of albumin, with maximum albumin transfer at 90 μM. Fatty acid treatment resulted in the increased appearance of cytosolic lipid droplets. Activities of the membrane‐bound enzymes, angiotensin‐converting enzyme (ACE), and Ca2+‐ATPase increased steadily with increasing time of cell exposure to 90 μM 18:2, reaching significance at 24 hr. Treatment of endothelial cultures with up to 120 μM 18:2 did not cause cytotoxicity, as evidenced by a nonsignificant change in cellular release of [3H]‐adenine. Incubation of 18:2‐supplemented serum‐containing culture media with 1000 μM 18:2 at 37°C for up to 48 hr did not result in formation of autooxidation products. These results suggest that 18:2 itself, and not its oxidation products, plays a major role in disrupting endothelial barrier function.
Effects of isoflurane on the Dnase I activity in an isolated enzyme preparation and on the Dnase I‐G actin complex
Authors: Reitz Manfred , Von Pfeil Andrea , Hundt Ferdinand , Lanz Egon 
Published: October 2006

AbstractEffects of isoflurane on the DNase I activity in an isolated enzyme preparation and in the DNase I‐globular (G) actin complex were investigated. DNase I, DNase I‐G actin complex, and G actin were exposed to various (0.2–4.0 vol%) isoflurane concentrations for 180 min. Thereafter, DNase I activity was determined. DNase I activity was inhibited in relation to time and concentration of isoflurane exposure. At concentrations ranging from 0.2 to 1.0 vol% of isoflurane inactive DNase I was activated in the DNase I‐G actin complex. The DNase I inhibitor G actin showed a reduced capability to inhibit DNase I following isoflurane exposure. Albumin can inhibit the DNase I inactivation possibly by competition in the reactions between DNase I/albumin and isoflurane. After exposure to isoflurane the absorption maximum of DNase I was identical with the absorption maximum of heat‐denaturated DNase I. The results suggest a mechanism by which isoflurane may affect DNA in an indirect way at concentrations to which the patient is exposed during clinical anesthesia.
Association of microcystin‐LR and its biotransformation product with a hepatic‐cytosolic protein
Authors: Robinson Nancy A. , Matson Charles F. , Pace Judith G. 
Published: October 2006

AbstractMicrocystin‐LR (MCYST‐LR), a cyclic peptide hepatotoxin, associates with high‐molecular‐weight, liver cytosolic components. Repetitive cycles of heat denaturation and pronase digestion released 80 ± 6% of the bound radiolabel from these components, parent toxin (22%), and two biotransformation products, with high‐performance liquid chromatography (HPLC) retention times of 6.7 (52%) and 5.6 (13%) min. Both parent and the biotransformed (6.7 min) toxin appeared to be covalently bound to a monomeric protein of molecular weight 40,000 (protein plus radiolabeled toxin). Binding and biotransformation reactions were time‐ and temperature‐dependent and did not require endogenous molecules <6,000 daltons. The binding appeared to be saturable with a maximum of 20 pmol MCYST‐LR bound per mg protein. The binding protein(s) and biotransformation activity were present in rat liver, brain, kidney, heart, lung, small intestine, large intestine, testes, skeletal muscle, and to a lesser extent, in fat. Okadaic acid, a specific protein phosphatase inhibitor, showed a concentration‐dependent inhibition of [3H]MCYST‐LR binding to hepatic cytosol. The molecular weight and organ distribution of the binding protein(s), and inhibition of binding by okadaic acid were consistent with one of the binding sites being the catalytic subunit of protein phosphatase type 2A.
Role of cytochrome P‐450 in ochratoxin a‐stimulated lipid peroxidation
Authors: Omar Rabeea F. , Rahimtula Anver D. , Bartsch Helmut 
Published: October 2006

AbstractThe role of cytochrome P‐450 in the stimulation of lipid peroxidation by the nephrotoxic mycotoxin ochratoxin A has been investigated. Ochratoxin A was previously shown to markedly stimulate lipid peroxidation in a reconstituted system consisting of phospholipid vesicles, NADPH‐cytochrome P‐450 reductase, Fe3+, ethylenediaminetetra‐acetic acid (EDTA), and reduced nicotinamide adenine dinucleotide phosphate (NADPH). We now show that purified cytochrome P‐450IIB1 could effectively replace EDTA in stimulating lipid peroxidation suggesting that it could mediate the transfer of electrons from NADPH to Fe3+. Cobalt protoporphyrin is known to cause an extensive and long‐lasting depletion of hepatic cytochrome P‐450 in rats, and it has been used to evaluate the role of hepatic cytochrome P‐450 in xenobiotic metabolism and toxicity. We have observed that microsomes isolated from livers of cobalt protoporphyrin‐pretreated rats underwent ochratoxin A‐dependent lipid peroxidation much more slowly than control microsomes. Also, the level of ethane exhaled (an index of in vivo lipid peroxidation) on ochratoxin A administration was much lower in cobalt protoporphyrin‐pretreated rats than in control rats. Taken together, these results provide evidence for the stimulatory role of cytochrome P‐450 in ochratoxin A‐induced lipid peroxidation in a reconstituted system and strongly implicate its role in microsomal and in vivo ochratoxin A‐induced lipid peroxidation.
Acrylonitrile interaction with testicular DNA in rats
Authors: Ahmed Ahmed E. , Abdel‐Rahman Sherif Z. , Nour Deen Amr M. ‐Al 
Published: October 2006

AbstractIn the present study we report the in vivo interaction of acrylonitrile (VCN) with testicular tissue in rats. Covalent binding of radioactivity to testicular tissue DNA was examined for a period of 72 hr after a single oral dose (46.5 mg/kg) of [2, 3‐14C] VCN. Maximal covalent binding was observed at 0.5 hr (8.9 μmol VCN equivalent/mol nucleotide). Binding decreased gradually thereafter but was still detected (2.5 μmol VCN equivalent/mol nucleotide) at 72 hr following VCN administration. Further, we examined the effects of VCN on DNA synthesis and repair in the testes of rats following a single oral dose (46.5 mg/kg) of VCN to clarify the impact of the covalent binding observed on the testicular genetic material. A significant decrease in DNA synthesis (80% of control) was observed at 0.5 hr after treatment. At 24 hr following acrylonitrile administration, testicular DNA synthesis was severely inhibited (38% of control). Testicular DNA repair was increased 1.5‐fold at 0.5 hr and more than 3.3‐fold at 24 hr following treatment with VCN. These results suggest that VCN can act as a multipotent genotoxic agent by alkylating DNA in testicular tissue and may affect the male reproductive function by interfering with testicular DNA synthesis and repair processes.
Lack of evidence for perfluorodecanoyl‐ or perfluorooctanoyl‐coenzyme a formation in male and female rats
Authors: Kuslikis Benedict I. , Vanden Heuvel John P. , Peterson Richard E. 
Published: October 2006

AbstractPerfluorodecanoic (PFDA) and perfluorooctanoic (PFOA) acids belong to the structurally diverse group of compounds known to cause peroxisomal proliferation. It has been hypothesized that the common mode of action of these compounds is that they act through an activated coenzyme A (CoA) thioester. Using rat liver microsomal and isolated rat hepatocyte incubation conditions that were effective in producing a COA conjugate of clofibric acid, no corresponding COA derivative could be found for either PFDA or PFOA.
Effect of endrin on the hepatic distribution of iron and calcium in female sprague‐dawley rats
Authors: Bagchi D. , Bagchi M. , Hassoun E. , Stohs S. A. 
Published: October 2006

AbstractThe distribution of iron and calcium in hepatic subcellular fractions of female rats treated with endrin (1, 2, 3, 4, 10, 10‐hexachloro‐6, 7‐epoxy‐1, 4, 4α, 5, 6, 7, 8, 8α‐octahydroendo, endo‐1, 4:5, 8‐dimethanonaphthalene) was determined. Endrin in corn oil was administered orally to rats in single doses of 3, 4.5, or 6 mg/kg, and the animals were killed at 0, 12, 24, 48, or 72 hr posttreatment. Iron and calcium were determined by atomic absorption spectroscopy. The administration of endrin increased the iron content of mitochondria and decreased the iron content of microsomes and nuclei. Significant increases occurred in the calcium content of mitochondria, microsomes, and nuclei. Thus, the results indicate that with respect to the subcellular distribution of iron and calcium, endrin produces differential effects. Vitamin E succinate administration partially prevented the endrin‐induced hepatic alterations in iron and calcium homeostasis. Endrin also produced dose‐ and time‐dependent increases in the liver and spleen weight/body weight ratios, while decreasing the thymus weight/body weight ratios. The altered distribution of calcium and iron may contribute to the broad range of effects of endrin.
Modifiers of mercaptopyruvate sulfurtransferase catalyzed conversion of cyanide to thiocyanate in vitro
Authors: Wing David A. , Baskin Steven I. 
Published: October 2006

AbstractThe enzyme mercaptopyruvate sulfurtransferase appears to play an important role in the in vivo detoxification of cyanide. It does so by transferring sulfur to cyanide to produce thiocyanate, which is less toxic and may be excreted through the kidney. Several compounds were tested for their ability to affect the rate of enzyme catalyzed thiocyanate formation in vitro. The studies were carried out using both a partially purified bovine kidney extract and a highly purified enzyme preparation. Hypotaurine and methanesulfinic acid doubled sulfurtransferase activity in the partially purified extract at 30 mM, but inhibited the purified enzyme to 57% (hypotaurine) and 27% (methanesulfinic acid) of control activity at the same concentration. Pyruvate, phenylpyruvate, oxobutyrate, and oxoglutarate each inhibited the extract and purified forms of mercaptopyruvate sulfurtransferase. Phenylpyruvate was the most effective inhibitor, reducing activity to 0.2% of control values in the extract, and 11% of control values for purified MPST when added to the reaction at 30 mM. Other compounds tested (see Table 1) had a negligible effect on sulfurtransferase activity. A heat stable cofactor was found in boiled kidney extract which stimulated sulfurtransferase activity in the extract but inhibited sulfurtransferase activity in the purified enzyme, as was observed for hypotaurine and methanesulfinate. The boiled extract had no thiocyanate forming activity of its own. The cofactor operated in synergy with methanesulfinate, but independently of hypotaurine.
Differential effects of paraoxon on the M3 muscarinic receptor and its effector system in rat submaxillary gland cells
Authors: Abdallah Elsayed A. M. , Jett David A. , Eldefrawi Mohyee E. , Eldefrawi Amira T. 
Published: October 2006

AbstractThe effects of the organophosphorus anticholinesterase paraoxon on the binding of radioactive ligands to the M3 subtype of the muscarinic receptor and receptor‐coupled synthesis of second messengers in intact rat submaxillary gland (SMG) cells were investigated. The binding of [3H]quinuclidinyl benzilate ([3H]QNB) was most sensitive to atropine and the M3‐specific antagonist 4‐DAMP followed by pirenzepine and least sensitive to the cardioselective M2 antagonist AFDX116. This, and the binding characteristics of [3H]4‐DAMP, confirmed that the muscarinic receptors in this preparation are of the M3 subtype. Activation of these muscarinic receptors by carbamylcholine (CBC) produced both stimulation of phosphoinositide (PI) hydrolysis and inhibition of cAMP synthesis, suggesting that this receptor subtype couples to both effector systems.Paraoxon (100 μM) reduced Bmax of [3H]4‐DAMP binding from 27 ± 4 to 13 ± 3 fmol/mg protein with nonsignificant change in affinity, suggesting noncompetitive inhibition of binding by paraoxon. Like the agonist CBC, paraoxon inhibited the forskolininduced cAMP formation in SMG cells with an EC50 of 200 nM, but paraoxon was > 500 fold more potent than CBC. However, while the inhibition by CBC was counteracted by 2 μM atropine, that by paraoxon was unaffected by up to 100 μM atropine. It suggested that this effect of paraoxon was not via binding to the muscarinic receptor. Paraoxon did not affect β‐adrenoreceptor function in the preparation, since it did not affect the 10 μM isoproterenol‐induced cAMP synthesis, which was inhibited totally by 10 μM propranolol and partially by CBC. Paraoxon had a small but significant effect on CBC‐stimulated PI metabolism in the SMG cells. It is suggested that paraoxon binds to two different sites in these SMG cells. One is an allosteric site on the M3 muscarinic receptor which affects ligand binding and may modulate receptor function. The other site may be on the Gi proteinadenylyl cyclase system, and produces CBC‐like action, that is, inhibition of the forskolin‐stimulated [3H]cAMP synthesis, and is unaffected by atropine inhibition of the muscarinic receptor. This adds to the complexity of paraoxon actions on muscarinic receptors and their effector systems.
The role of calcium ions for the expression of ricin toxicity in cultured macrophages
Authors: Naseem Syed M. , Wellner Robert B. , Pace Judith G. 
Published: October 2006

AbstractRicin toxin, which consists of two distinct polypeptide moieties, A and B chains, is cytotoxic to the cultured macrophage cell line, J774A.1. Ricin is a protein synthesis inhibitor, and incubating macrophages for 4 hours with ricin (1 pM to 10 nM) in standard medium containing calcium and magnesium inhibited 3H‐leucine incorporation into protein (97%, at 1 nM ricin). However, in Ca2+‐free medium, protein synthesis was inhibited only 19%. EGTA pretreatment (to deplete intracellular calcium) also partly protected cells from protein synthesis inhibition, in spite of added calcium (2 mM) in the incubation medium. Decreased toxicity in the absence of extracellular calcium resulted from decreased toxin binding. Adding or deleting Mg2+ did not affect protein synthesis or binding of 125I‐ricin in cultured macrophages. We conclude that calcium is required for ricin to exert its inhibitory effect on protein synthesis in cultured macrophages.
Additive effects and potential inhibitory mechanism of some common aromatic pollutants on in vitro mitochondrial respiration
Authors: Beach Andrew C. , Harmon James 
Published: October 2006

AbstractThe in vitro toxicity of multiple hydrophobic compounds was the focus of this study. A mitochondrial respiratory assay, sensitive to perturbations caused by hydrophobic chemicals, was utilized to measure the effects of individual aromatic hydrocarbon pollutants and their mixtures on mitochondrial respiratory function. Benzene, naphthalene, acenaphthene, and 1‐chloronaphthalene, common industrial solvents shown to interact additively in vivo, were evaluated using this in vitro assay system. Mitochondrial respiration was inhibited 50% (EC50) by 525 ppm (6.7 mM) benzene, 15 ppm (117 μM) naphthalene, 3.9 ppm (25.5 μM) acenaphthene, or 3.8 ppm (23.4 μM) 1‐chloronaphthalene. NADH:O2 oxidoreductase (NADH → O2), NADH: ubiquinone oxidoreductase, and ubiquinol:O2 oxidoreductase activities were inhibited by all four compounds, whereas succinate:O2 oxidoreductase, cytochrome c oxidase, and duroquinol: O2 oxidoreductase activities were not inhibited. Inhibition of mitochondrial respiration occurred at the level of ubiquinone (coenzyme Q10) for all four aromatic hydrocarbons. The ultraviolet absorbance spectrum of isolated Q10 was also altered by naphthalene, acenaphthene, or 1‐chloronaphthalene, suggesting a specific interaction between that component of the respiratory chain and these aromatic hydrocarbons. Inhibition by a mixture of 2, 3, or 4 of the compounds tested was additive, reflecting a summation effect of each compound present in the mixture. This additive nature is consistent with previously reported effects of these compounds in vivo and with compounds having similar modes of action. The similar mode of action in vitro is a specific interaction with coenzyme Q10, not a generalized membrane perturbation as speculated to occur in vivo, and is the likely mechanism for the observed additive toxicity.
Regional distribution of neuropeptide‐degrading enzyme activity in the rat brain: Effects of subacute exposure to carbon disulfide
Authors: De Gandarias J. M. , Echevarría E. , Irazusta J. , Casis O. , Casis L. 
Published: October 2006

AbstractCarbon disulfide, a volatile solvent, is widely used in industry. It has been demonstrated that it causes several neuropsychological symptoms. However, the neurochemical basis of its neurotoxic effect is relatively unknown. In this paper we have measured the effect of subacute i.p. administration on neutral and basic aminopepti‐dase activities in discrete zones of the rat brain using lysine‐ and leucine‐2‐naphtylamides as substrates. Neutral aminopeptidase activity showed a significant decrease in the thalamus and cerebellum with marked (not significant) changes in the hypothalamus, hippocampus, medulla, and occipital cortex. There were no changes in basic ami‐nopeptidase activity. It is suggested that amino‐peptidase activity could play a role in carbon disulfide neurotoxic action in the aforementioned regions by generating changes in several neuropeptide levels.