bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxic effects of fatty acid anilides on the oxygen defense systems of guinea pig lungs and erythrocytes
Authors: Mukherjee Shyamali , Ghos Sukla , Rodgers Lisa , Nayyar Tultul , Desai Usha , Das Salil K. 
Published: October 2006

AbstractToxic oil syndrome (TOS) is caused by ingestion of denatured edible oils. Even though the etiology and pathogenesis of this disease are not fully known, it is quite clear that generation of free radicals caused by ingestion of fatty acid anilides is responsible for the pathogenetic mechanism in many TOS patients. Fatty acid anilides may also alter the free radical status of lungs and erythrocytes; this possibility may shed some light on understanding toxic oil syndrome. The present study describes the effects of oral administration of fatty acid anilides on the activities of major enzymes involved in the oxygen defense systems of lungs and erythrocytes. Feeding fatty acid anilides caused an increase in the superoxide dismutase (SOD) activity in erythrocytes, whereas it caused a decrease in the SOD activity in lungs. GSH‐Px activity was not significantly changed in erythrocytes but was decreased in lungs. Although the activity of catalase was increased only by a higher dose in the erythrocytes, it was not affected in the lung at any dosage. Even though the ingestion of fatty acid anilides caused an increase in the SOD activity in the erythrocytes and a decrease in the SOD activity in the lungs, there was an increase in the lipid peroxidation in both cases. The increase in lipid peroxidation in erythrocytes is probably caused by the accumulation of H2O2, and that in the lungs is due to the accumulation of superoxide anion.
Aluminum alters calcium transport in plasma membrane and endoplasmic reticulum from rat brain
Authors: Mundy William R. , Kodavanti Prasada Rao S. , Dulchinos Victoria F. , Tilson Hugh A. 
Published: October 2006

AbstractCalcium is actively transported into intracellular organelles and out of the cytoplasm by Ca2+/Mg2+‐ATPases located in the endoplasmic reticulum and plasma membranes. We studied the effects of aluminum on calcium transport in the adult rat brain. We examined 45Ca‐uptake in microsomes and Ca2+‐ATPase activity in microsomes and synaptosomes isolated from the frontal cortex and cerebellum of adult male Long‐Evans rats. ATP‐dependent45Ca‐uptake was similar in microsomes from both brain regions. The addition of 50‐800 μM AICI3 resulted in a concentration‐dependent inhibition of 45Ca‐uptake. Mg2+‐dependent Ca2+‐ATPase activity was significantly lower in synaptosomes compared to microsomes in both frontal cortex and cerebellum. In contrast to the uptake studies, AICI3 stimulated Mg2+‐dependent Ca2+‐ATPase activity in both microsomes and synaptosomes from both brain regions. To determine the relationship between aluminum and Mg2+, we measured ATPase activity in the presence of increasing concentrations of Mg2+ or AICI3. Maximal ATPase activity was obtained between 3 and 6 mM Mg2+. When we substituted AICI3 for Mg2+, ATPase activity was also stimulated in a concentration‐dependent manner, but to a greater extent than with Mg2+. One interpretation of these data is that aluminum acts at multiple sites to displace both Mg2+ and Ca2+, increasing the activity of the Ca2+‐ATPase, but disrupting transport of calcium.
Molecular interaction of [2,3‐14C] acrylonitrile with DNA in gastric tissue of rat
Authors: Abdel‐Rahman Sherif Z. , Nouraldeen Amr M. , Ahmed Ahmed E. 
Published: October 2006

AbstractAcrylonitrile (VCN) is used extensively in polymer industries, and is known to induce gastric cancer following oral administration, A paucity of information exists regarding the mechanism(s) by which acrylonitrile induces gastric neoplasia. The time course for uptake of radioactivity by gastric tissue and covalent binding of [2,3‐14C] VCN or its metabolites to gastric DNA were determined following a single oral dose of 46.5 mg/kg. The rates of DNA synthesis and repair, as measured by unscheduled DNA synthesis in the gastric tissue of VCN‐treated rats, were also studied. Maximum tissue uptake and covalent binding of radioactivity to gastric DNA were observed at 15 minutes following [2,3‐14C] VCN administration. At 6 hours following VCN administration, significant inhibition (37% of control) in gastric replicative DNA synthesis was observed. A rebound followed by an increase (211% of control) in replicative DNA synthesis was observed at 24 hours. A three‐fold elevation in unscheduled DNA synthesis was observed at 24 hours following treatment with VCN. These results indicate that VCN or its metabolites irreversibly interact with gastric DNA, causing DNA damage. The results also indicate that the delayed VCN‐induced DNA repair, determined as unscheduled DNA synthesis, is inefficient for the removal of the resulting DNA lesions.
Cyanide induces protein kinase C translocation: Blockade by NMDA antagonists
Authors: Rathinavelu A. , Sun P. , Pavlakovic G. , Borowitz J. L. , Isom G. E. 
Published: October 2006

AbstractActivation and translocation of protein kinase C (PKC) during KCN‐induced histotoxic hypoxia was studied in rat brain slices prepared from cerebellum, hippocampus, and cortex. Treatment with 1–10 mM KCN produced a significant increase in PKC translocation and enzyme activity in the particulate fraction of cerebellar and hippocampal slices. In cortical slices, PKC activity was not affected by cyanide treatment. The membrane‐associated PKC activity reached a maximum 30 minutes after incubation with KCN and remained elevated up to 60 minutes in both the hippocampus and cerebellum. Pretreatment with MK‐801 and APV, specific NMDA receptor antagonists, blocked the cyanide‐stimulated translocation in the hippocampus and cerebellum, whereas CNQX, an AMPA/kainate receptor antagonist, did not alter the response. These results demonstrate that cyanide stimulates PKC activation and translocation from the cytosol to membranes in select brain areas and NMDA receptor activation mediates this process.
Differential modulation of hepatic cytochrome P‐450 enzymes in rat and syrian hamster by 4′‐trifluoromethyl‐2,3,4,5‐tetrachlorobiphenyl
Authors: Bani Marie‐Hélène , Narbonne Jean‐Franco̧is , Fukuhara Morio , Ushio Fusao , Robertson Larry W. 
Published: October 2006

AbstractThe effects of a single injection (40 mg/kg) of 4′‐trifluoromethyl‐2,3,4,5‐tetrachlorobiphenyl (CF3) on hepatic cytochrome P‐450 monooxygenases were assessed in rat and syrian hamster. The CF3 treatment significantly increased the total amount of cytochrome P‐450 in both species. In rats, CF3 treatment caused marked increases in ethoxyresorufin O‐deethylase (EROD), arylhydrocarbon hydroxylase (AHH), and testosterone 7α‐hydroxylase activities but significantly reduced the activities of benzphetamine N‐demethylase (BzND), erythromycin N‐demethylase (ErND), testosterone 6β, 16α, and 16β‐hydroxylases, and formation of androstenedione. Administration of CF3 to hamsters strongly induced the activities of EROD, AHH, BzND, testosterone 15α, and 16α‐hydroxylases, and androstenedione production, whereas ErND, testosterone 6β, and 7α‐hydroxylases were decreased. Administration of CF3 to rats induced the CYP1A family proteins and CYP2A1, while CF3 reduced the level of CYP2B1, and, to a lesser extent, of CYP6β2. In hamsters, CF3 treatment significantly induced the CYP1A2, CYP2A1, CYP2A8, and CYP2B1 isozymes, whereas the CYP6β2 level was decreased. The ability of hepatic microsomes to activate aflatoxin B1 and benzo(a)pyrene was elevated by CF3 treatment in hamsters, while activation of aflatoxin B1 was decreased in microsomes from CF3‐treated rats. These results showed differences in the CF3‐induced pattern of rat and hamster cytochrome P‐450 monooxygenases.
Evidence for two functionally distinct forms of the human Ah receptor
Authors: Perdew Gary H. , Hollenback Clayton E. 
Published: October 2006

AbstractThe Ah receptor (AhR) was visualized using monoclonal antibody Rpt 1 on protein blots of HeLa cell cytosol; two bands were detected at 104 and 106 kDa. The photoaffinity ligand, 2‐azido‐3‐[125I]iodo‐7,8‐dibromodibenzo‐p‐dioxin, was added to HeLa cells in culture, and after 1 hour the cells were UV irradiated. Cytosolic and high salt nuclear preparations were isolated and subjected to sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS‐PAGE), followed by transfer of the protein to membrane. The AhR was visualized on the membrane, revealing two bands. Alignment of an autoradiogram with the membrane revealed that only the 106 kDa (upper) band was photoaffinity labeled. The nuclear fraction contained only the photoaffinity‐labeled 106 kDa form of the AhR. The 104 kDa AhR does not appear to be a proteolytic product of the 106 kDa form. Cyanogen bromide fragmentation revealed that both forms contain the same size N‐terminal fragment. Sucrose density gradient analysis of HeLa cell cytosol indicated that both forms cosedimented at 9 S. Both the 106 and 104 kDa AhR bands were detected in four different human cell lines. Together, these results would indicate that the AhR in human cell lines exists in two distinct forms.
Lipoxygenase‐mediated glutathione oxidation and superoxide generation
Authors: Roy Partha , Sajan Mini P. , Kulkarni Arun P. 
Published: October 2006

AbstractSoybean lipoxygenase‐mediated cooxidation of reduced glutathione (GSH) and concomitant superoxide generation was examined. The oxidation of GSH was dependent on the concentration of linoleic acid (LA), GSH, and the enzyme. The optimal conditions to observe maximal enzyme velocity included the presence of 0.42 mM LA, 2 mM GSH, and 50 pmole of enzyme/mL. The GSH oxidation was linear up to 10 minutes and exhibited a pH optimum of 9.0. The reaction displayed a Km of 1.49 mM for GSH and Vmax of 1.35 ± 0.02 μmoles/min/nmole of enzyme. Besides LA, arachidonic and γ‐linolenic acids also supported the lipoxygenase‐mediated GSH oxidation. Hydrogen peroxide and 13‐hydroperoxylinoleic acid supported GSH cooxidation, but to a very limited extent. Oxidized glutathione (GSSG) was identified as the major product of the reaction based on the depletion of nicotinamide‐adenine dinucleotide 3′‐phosphate (NADPH) in the presence of glutathione reductase. The GSH oxidation was accompanied by the reduction of ferricytochrome c, which can be completely abolished by superoxide dismutase (SOD), suggesting the generation of superoxide anion radicals. Under optimal conditions, the rate of superoxide generation (measured as the SOD‐inhibitable reduction of ferricytochrome c) was 10 ± 1.0 nmole/min/nmole of enzyme. These results clearly suggest that lipoxygenase is capable of oxidizing GSH to GSSG and simultaneously generating superoxide anion radicals, which may contribute to oxidative stress in cells under certain conditions.
Inhibition of lecithin:Cholesterol acyltransferase activity in human blood plasma by cigarette smoke extract and reactive aldehydes
Authors: Chen Chen , Loo George 
Published: October 2006

AbstractCigarette smoking is a risk factor for atherosclerosis. It is conceivable that reactive chemical components in cigarette smoke may adversely affect reverse cholesterol transport at the level of lecithin:cholesterol acyltransferase (LCAT) and promote atherogenesis. Hence, the effect of cigarette smoke extract (CSE) on the activity of LCAT in human plasma was studied. When incubated with plasma, CSE caused both concentration‐ and time‐dependent losses of LCAT activity. Addition of glutathione, but not ascorbate, to plasma prevented loss of LCAT activity caused by CSE. Incubation of plasma with some reactive aldehydes known to be present in cigarette smoke also inhibited LCAT activity. Among five aldehydes tested, acrolein was the strongest inhibitor of LCAT, with complete enzyme inhibition occurring at 1 mM. Acetaldehyde was the weakest inhibitor of LCAT, with 85% enzyme inhibition at 50 mM. Hexanal, formaldehyde, and malondialdehyde completely inhibited LCAT activity at 10, 50, and 50 mM, respectively. When plasma was incubated with 1 mM acrolein in the presence of 2.5 mM glutathione or dihydrolipoic acid, 100 and 57% of LCAT activity, respectively, remained after incubation. This finding suggests that reactive aldehydes may form adducts with certain free sulfhydryl groups functioning in the active site of LCAT to inhibit enzyme activity. It is concluded that reactive aldehydes are at least partially responsible for the reduction in LCAT activity in plasma treated with CSE.
Stereoselective sulfoxidation of the pesticide methiocarb by flavin‐containing monooxygenase and cytochrome P450‐dependent monooxygenases of rat liver microsomes. Anticholinesterase activity of the two sulfoxide enantiomers
Authors: Buronfosse T. , Moroni P. , Benoǐt E. , Rivière J. L. 
Published: October 2006

AbstractEvidence based on thermal lability and enzyme inhibition data suggests that the sulfoxidation of methiocarb (an N‐methylcarbamate insecticide) by rat liver microsomes is catalyzed by flavin‐containing monooxygenase(s) (FMO) and by cytochrome(s) P450 (P450). In control rats, the relative proportion is ca. 50% P450:50% FMO. Stereoselective formation of methiocarb sulfoxide from the corresponding sulfide has also been examined to compare the enantioselectivity of the two different enzyme systems. Only the FMO‐dependent sulfoxidation presents a high stereoselectivity with an enantiomeric excess of 88% in favor of the (A)‐enantiomer. Pretreatment of rats with different P450 inducers such as phenobarbital, 3‐methylcholanthrene, dexamethasone, and pyrazole did not affect, or decreased, the rate of methiocarb sulfoxidation. Stereoselectivity of the reaction was modified, mainly because of changes in the relative involvement of FMO and P450 in sulfoxidase activity in pretreated animals. The acetylcholinesterase inhibition properties of methiocarb and its main metabolites were also investigated. Racemic methiocarb sulfoxide was slightly less inhibitory (Ki = 0.216 μM−1· min−1) than methiocarb, but a 10‐fold difference was observed between the bimolecular rate constants found for the two sulfoxides produced (0.054 and 0.502 μM−1·min−1 for the (A) and (B) enantiomers, respectively). © 1995 John Wiley & Sons, Inc.
Exposure to polychlorinated biphenyls causes endothelial cell dysfunction
Authors: Toborek Michal , Barger Steven W. , Mattson Mark P. , Espandiari Parvaneh , Robertson Larry W. , Hennig Bernhard 
Published: October 2006

AbstractEnvironmental chemicals, such as polychlorinated biphenyls (PCBs), may be atherogenic by disrupting normal functions of the vascular endothelium. To investigate this hypothesis, porcine pulmonary artery‐derived endothelial cells were exposed to 3,3′,4,4′‐tetrachlorobiphenyl (PCB 77), 2,3,4,4′,5‐pentachlorobiphenyl (PCB 114), or 2,2′,4,4′,5,5′‐hexachlorobiphenyl (PCB 153) for up to 24 hours. These PCBs were selected for their varying binding avidities with the aryl hydrocarbon (Ah) receptor and differences in their induction of cytochrome P450. PCB 77 and PCB 114 significantly disrupted, in a dose‐dependent manner, endothelial barrier function by allowing an increase in albumin transfer across endothelial monolayers. These PCBs also contributed markedly to cellular oxidative stress, as measured by 2,7‐dichlorofluorescin (DCF) fluorescence and lipid hydroperoxides, and caused a significant increase in intracellular calcium ([Ca2+]i) levels. Enhanced oxidative stress and [Ca2+]i in PCB 77‐ and PCB 114‐treated cells were accompanied by increased activity and content of cytochrome P450 1A and by a decrease in the vitamin E content in the culture medium. In contrast to the effects of PCB 77 and PCB 114, cell exposure to PCB 153 had no effect on cellular oxidation, [Ca2+]i, or endothelial barrier function. These results suggest that certain PCBs may play a role in the development of atherosclerosis by causing endothelial cell dysfunction and a decrease in the barrier function of the vascular endothelium. It is possible that interaction of PCBs with the Ah receptor and activation of the cytochrome P450 1A subfamily are involved in this pathology. © 1995 John Wiley & Sons, Inc.
DNA single‐strand breakage in mammalian cells induced by redox cycling quinones in the absence of oxidative stress
Authors: Morgan Winston A. 
Published: October 2006

AbstractQuinone‐induced cell death is often attributed to oxidative stress during which the formation of DNA strand breaks is thought to play an important role. In this study, extensive DNA damage was observed in human chronic myelogenous leukemic cells (K562) exposed for 15 minutes to low concentrations (15–100 μM) of the redox cycling quinones 2,3‐dimethoxy‐1,4‐naphthoquinone (2,3‐diOMe‐1,4‐NQ) and menadione. However, DNA strand breakage and cell death could not be attributed to oxidative stress as the intracellular level and redox status of the reducing equivalents NADP(H) and GSH were unaffected. The intracellular level of NAD+ was found to correlate well with the extent of DNA repair (r = 0.93, P < 0.02) and cell proliferation (r = 0.96, P < 0.01) in cells exposed to the quinones. In contrast, a significant decrease in the level of intracellular ATP was only observed in cells exposed to menadione (50–100 μM). These results suggest that redox cycling quinones are capable of inducing DNA damage in mammalian cells by a mechanism that does not involve oxidative stress. Following DNA damage, cell death is dependent on the availability of NAD+, which may be key to the rapid repair of strand breaks. © 1995 John Wiley & Sons, Inc.
Specificity studies of 3‐mercaptopyruvate sulfurtransferase
Authors: Porter Dale W. , Baskin Steven I. 
Published: October 2006

Abstract3‐Mercaptopyruvate sulfurtransferase (E.C. 2.8.1.2; MST) is an enzyme believed to function in the endogenous cyanide (CN) detoxification system because it is capable of transferring sulfur from 3‐mercaptopyruvate (3‐MP) to CN, forming the less toxic thiocyanate (SCN). To date, 3‐MP is the only known sulfur‐donor substrate for MST. In an effort to increase the understanding of what chemical properties of 3‐MP affect its utilization as a substrate, in vitro enzyme kinetic studies of MST were conducted using two mercaptic acids that are structurally related to 3‐MP. Neither of these compounds was able to serve as a sulfur‐donor substrate for MST. Inhibitor studies determined that 3‐mercaptopropionic acid did not affect the Km of MST for 3‐MP but did decrease Vmax and, thus, was determined to be a noncompetitive inhibitor. Alternatively, 2‐mercaptopropionic acid 2‐MPA decreased Km and Vmax and was determined to be an uncompetitive inhibitor of MST with respect to 3‐MP. These data indicate that the α‐keto group of 3‐MP is necessary for its utilization as a substrate, and the inhibitor studies suggest that the position of the sulfur may also affect the binding of these compounds to the enzyme. These observations increase the understanding of what factors can affect the utilization of a compound as a sulfur‐donor substrate for MST and may aid in the development of alternative sulfur‐donor substrates for MST. © 1996 John Wiley & Sons, Inc.
The effect of nitrogen dioxide exposure on the release of surfactant isolated from neonatal rabbit type II pneumocytes in culture
Authors: Knight Matthew , Sekharam Madhavi , Patel Jay 
Published: October 2006

AbstractNitrogen dioxide (NO2) is a well‐known environmental air toxin, produced from a variety of sources, including cigarette smoke. Because of the growing knowledge of the harmful effects of passive smoking on children, we decided to study the effect of NO2 exposure on the release of surfactant from isolated neonatal type II pulmonary epithelial cells. After isolation from 1 to 4 day old rabbits, type II epithelial cells were allowed to adhere for 18 hours, washed, media changed, and were exposed to either 5% CO2 in room air or NO2, 5 ppm, for 2 hours (all results mean ± sd; comparisons, paired t‐test). There was no difference in cell number or viability prior to exposure. Cells exposed to NO2 had an increase in LDH release [LDH activity in media/(LDH in media + cells) x 100], air 12.6 ± 2.2%, NO2 21.7 ± 3.7%, (p < 0.05). NO2‐exposed cells also had an increase in total phospholipid (μg/cell culture dish) in media compared to air exposed, air 170.13 ± 7.54, NO2 195.15 ± 11.2, (p < 0.05). 3H‐choline incorporation as a precursor to disaturated phosphati‐dylcholine (DSPC) was also conducted during exposure to either air or NO2. Incorporation of 3H‐choline into surfactant lipid was increased in media from cells after NO2 exposure compared to air, 58.23 ± 15.16 air, 76.81 ± 19.86 NO2 (cpm/μg protein; p < 0.05). These results show that 2 hours of 5 ppm NO2 exposure is associated with an increase in release of surfactant from neonatal type II cells in culture. © 1996 John Wiley & Sons, Inc.
Head morphology in perinatal dolphins: A window into phylogeny and ontogeny
Authors: Rauschmann Michael A. , Huggenberger Stefan , Kossatz, Lars S. , Oelschläger Helmut H.A. 
Published: October 2006

AbstractIn this paper on the ontogenesis and evolutionary biology of odontocete cetaceans (toothed whales), we investigate the head morphology of three perinatal pantropical spotted dolphins (Stenella attenuata) with the following methods: computer‐assisted tomography, magnetic resonance imaging, conventional X‐ray imaging, cryo‐sectioning as well as gross dissection. Comparison of these anatomical methods reveals that for a complete structural analysis, a combination of modern imaging techniques and conventional morphological methods is needed. In addition to the perinatal dolphins, we include series of microslides of fetal odontocetes (S. attenuata, common dolphin Delphinus delphis, narwhal Monodon monoceros). In contrast to other mammals, newborn cetaceans represent an extremely precocial state of development correlated to the fact that they have to swim and surface immediately after birth. Accordingly, the morphology of the perinatal dolphin head is very similar to that of the adult. Comparison with early fetal stages of dolphins shows that the ontogenetic change from the general mammalian bauplan to cetacean organization was characterized by profound morphological transformations of the relevant organ systems and roughly seems to parallel the phylogenetic transition from terrestrial ancestors to modern odontocetes. J. Morphol., 2006. © 2006 Wiley‐Liss, Inc.