Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Metallocenes”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed2000

Characterization of hepatic iron overload following dietary administration of dicyclopentadienyl iron (Ferrocene) to mice: cellular, biochemical, and molecular aspects.

A unique organic form of iron (dicyclopentadienyl iron; ferrocene) has been used to further elucidate specific hepatic histopathologic, biochemical, and molecular parameters associated with dietary iron overload. Male C57BL/6Ibg mice fed a diet containing 0.04-0.2% w/w ferrocene for 115 days displayed severe hepatic siderosis of hepatocytes accompanied by a 15-fold induction of nonheme iron content compared to control mice receiving a diet with normal amounts of iron. The ferrocene treatment led to significant increases in hepatocellular necrosis as measured by plasma alanine aminotransferase activity. Histological assessment of hepatic fibrosis revealed mild increases in collagen deposition localized with accumulations of hemosiderin primarily in centrilobular hepatocytes. Hepatic fibrosis was confirmed by measurement of hepatic hydroxyproline content that was increased 4-fold in ferrocene-fed animals compared to control animals not ingesting ferrocene. Hepatic siderosis was accompanied by significant increases in hepatic malondialdehyde content suggesting the ferrocene-induced iron burden initiated lipid peroxidation in vivo. Expression of the heavy-chain isoform of ferritin mRNA and protein measured in liver after ferrocene feeding was increased approximately 8- and 2-fold, respectively, compared to the appropriate controls. These results, using an organic form of iron fed to genetically well-characterized inbred mice, provide new additional insight into the specific molecular and biochemical events that occur in association with histopathologic changes initiated by iron-induced liver injury. These data support the hypothesis that peroxidation of cellular membrane lipids is an important mechanism involved in the toxicity of excess hepatic iron and possibly the initiation of liver fibrogenesis. The results presented here also provide novel in vivo evidence documenting the cellular modulation of ferritin in response to the toxic effects of hepatic iron overloading and iron-mediated oxidative stress.

Alanine Transaminase↗
PubMed1984

Ferricenium complexes: a new type of water-soluble antitumor agent.

The antitumor activity of a series of iron complexes, i.e., of ferrocene [Cp2Fe], of tetrachloroferrates(III) [R4N]+[FeCl4]-, and of ferricenium complexes [Cp2Fe]+X- (X- = [FeCl4]-, 1/2 [Cl3FeOFeCl3]2-, [H5Mo7O24]- X 2H2O, [2,4,6-(NO2)3C6H2O]-, or [CCl3COO]- X 2 CCl3COOH) was investigated against EAT in CF1 mice. Whereas ferrocene and the ammonium tetrachloroferrates(III) did not show recognizable tumor-inhibiting activity, such activity was exhibited by the water-soluble, salt-like ferricenium complexes; the best antineoplastic properties, with optimum cure rates of 100%, were found for ferricenium picrate and ferricenium trichloroacetate. The ferricenium compounds are the first iron complexes for which antineoplastic activity has now been shown. They represent a new type of antitumor agent insofar as they differ fundamentally from known inorganic and organometallic antitumor agents (a) by their ionic, salt-like character, which is responsible for their high water solubility, and (b) by the absence of a cis-dihalometal moiety; this moiety has been recognized as important for the intracellular action of other known inorganic cytostatics.

Animals↗
PubMed1984

Demonstration of electron-dense material in clear synaptic vesicles using cationic ferrocenyl compounds.

Electron-dense material in clear synaptic vesicles in rat cerebral cortex and neuromuscular junctions of frog cutaneous pectoris muscle was demonstrated by using ferrocenyl cationics. Electron-dense spots were usually attached to the inner surface of the vesicular membrane. Control experiments (treatment with Triton X-100 or cetylpyridinium chloride; enzyme digestion with trypsin, hyaluronidase, neuraminidase, sulfatase and beta-glucuronidase) suggested that the electron-dense material is a glycoprotein.

Animals↗
PubMed1992

Protection of guinea pigs against soman poisoning with ferrocene carbamate.

The protective effect of ferrocene carbamate pretreatment against soman poisoning was studied in guinea pigs. At doses corresponding to 1/20 x and 1/10 x LD50 of this carbamate a 20% and 45% decrease of the acetylcholinesterase in blood and brain, respectively, was obtained. In combination with additional pretreatment, diazepam, and therapy, HI-6 and atropine, the protective ratios (LD50 of soman in treated animals/LD50 of soman in untreated animals) were around 20 and 40, respectively. Animals pretreated with the high dose of the ferrocene carbamate that survived 10 x and 15 x LD50s of soman showed no remaining signs of poisoning after 24 h. Thus, the ferrocene carbamate afforded a better protection against soman than physostigmine. The explanation for this could be due to the properties of the ferrocene carbamate, not correlated to its cholinesterase inhibiting activity. This hypothesis is discussed.

Animals↗
PubMedDate not supplied

Aluminum but not iron treatment induces pro-oxidant events in the rat brain.

In an attempt to delineate the capacity of aluminum (Al) to promote pro-oxidant events, several indices of oxidative stress have been determined in brains and livers of rats exposed to an Al salt, either alone or in combination with an iron (Fe) compound. Treatment with Al over a 3-wk period increased both cortical levels of glutathione (GSH) and the rates of generation of reactive oxygen species (ROS). Dosing with an Fe compound resulted in no parallel changes, and concurrent exposure to Fe together with Al prevented these elevations. Both Fe and Al dosing elevated glutamine synthetase activity in the cortex. Levels of creatine kinase, another enzyme susceptible to oxidative stress, were also elevated in cortices of Al-treated rats. These data are in contrast to the changes found in liver fractions where exposure to Fe greatly enhanced hepatic pro-oxidant events as judged by changes in all three of the test indices used. Concurrent treatment with Al did not potentiate the pro-oxidant effects of Fe in liver. Al treatment had very minor effects on hepatic parameters of oxidative events. The results suggest that the presence of Al may exert deleterious pro-oxidant changes within the brain, which may be related to induction of oxidant species. These changes are tissue-specific and appear to be independent of any promotion of pro-oxidant status induced by exogenous Fe.

Aluminum↗
PubMed2001

Cyclic voltammetric simulation of electrochemically mediated enzyme reaction and elucidation of biosensor behaviors.

A cyclic voltammetric simulation that can be applied to an electrochemically mediated enzyme reaction involving any substrate and mediator concentration was developed. Concentration polarization of the substrate in the vicinity of an electrode was considered as well as mediator concentration. Reversible electrochemical reaction with one electron followed by an enzyme reaction with two electrons was modeled. The differential equations for the mediator and substrate were solved using digital simulation techniques. The calculated cyclic voltammograms showed prepeaks when there was a low substrate concentration, high mediator concentration, and high enzyme activity. The prepeak was experimentally observed in the case of an enzyme electrode co-immobilized with a redox polymer. The enzyme electrode loaded at high redox polymer and high enzyme content showed a prepeak at low substrate concentration in the cyclic voltammogram.

Biosensing Techniques↗
PubMed1986

An animal model of iron overload and its application to study hepatic ferritin iron mobilization by chelators.

Administration of 3,5,5-trimethylhexanoyl ferrocene in the diet of male Wistar rats results in a substantial increase in hepatic ferritin protein (greater than 2-fold) and of ferritin iron (4-8-fold). The iron-loading in liver, under the conditions used, appears to be essentially in parenchymal cells rather than in reticulo-endothelial cells. It is suggested that the model represents a useful system for the study of the potential efficacy of new iron chelators for the mobilization of hepatic storage iron. The ability of desferal (DFO) and of a new siderophore, desferrithiocin (DFT), to mobilize hepatic ferritin iron is observed in this model of iron overload. Desferrithiocin stimulates ferritin iron mobilization, when administered either by gavage or by intraperitoneal injection, whereas desferal is active intraperitoneally but inactive orally. Our studies lead to the conclusion that DFT merits further examinations, for its activity as an orally active iron chelator.

Administration, Oral↗
PubMed1992

Studies of in vivo iron mobilization by chelators in the ferrocene-loaded rat.

The oral efficacy of the oral iron chelators 1,2-dimethyl-3-hydroxypyrid-4-one (CP20), 1,2-diethyl-3-hydroxypyrid-4-one (CP94) and desferrioxamine B (DFO) has been compared with intraperitoneal DFO in an experimental model of iron overload with similar biochemical and biophysical characteristics to those observed for human genetic haemochromatosis. The hepatic iron stores in the ferrocene-loaded rat were relatively stable and did not decrease at the end of the loading period. In contrast, the iron dextran rat model showed a rapid depletion of its iron stores 2 weeks after cessation of intraperitoneal injection. When CP20 and CP94 were administered to the ferrocene-loaded rat model in combination with an iron-free diet there were significant decreases in (i) total homogenate iron and (ii) hepatic ferritin iron when compared to the iron-loaded rat receiving the iron-free diet alone. Desferrioxamine, when administered by gavage, only showed chelation of ferritin iron, while intraperitoneal injection of desferrioxamine showed significant depletion of iron both in the total homogenate and ferritin. Subcellular fractionation of the hepatic organelle clearly showed that where there was depletion of homogenate iron there was a net decrease in the lysosomal fraction, while changes in ferritin iron were reflected by decreases in the cytosolic iron content. Although no assessment of net iron excretion was made, we suggest that the use of this animal model should ascertain the site of chelation by iron chelators.

Animals↗
PubMed1993

Metabolism of iron from (3,5,5-trimethylhexanoyl)ferrocene in rats. A dietary model for severe iron overload.

The feeding of diets enriched with (3,5,5-trimethylhexanoyl)ferrocene (TMH-ferrocene) has been shown recently to produce a severe experimental iron overload in rats and has been considered as an adequate animal model for hereditary haemochromatosis in humans. We synthesized three 59Fe-labelled ferrocene compounds with different lipophilic characters (ferrocene, TMH-ferrocene, and 1,1'-bis(3,5,5-trimethylhexanoyl)ferrocene [(TMH)2-ferrocene]) and studied the metabolism of iron from these compounds in comparison with the hydrophilic ferrous sulphate in rats with iron deficiency, and normal and increased iron stores. The bioavailability of iron from TMH-ferrocene (whole body retention, 48% from a 5 mg Fe dose) was twice as high as from ferrocene and six times higher than from (TMH)2-ferrocene and ferrous sulphate. In contrast to the well-known iron salts (ferrous sulphate), the intestinal absorption of TMH-ferrocene iron was independent from the dose (1 or 5 mg Fe) and similar in iron-deficient and iron-loaded rats, indicating that the intestinal absorption of the TMH-ferrocene is not regulated by the body iron stores. After intestinal absorption, TMH-ferrocene iron in the portal blood is transported to the liver independently from transferrin. In contrast to absorbed ferrocene, iron from TMH-ferrocene is almost completely released from the hydrocarbon moiety within the liver. Depending on the body iron stores, TMH-ferrocene iron is then incorporated preferentially into haemoglobin (iron-deficient rats) or added to the iron stores in the liver (iron-loaded rats). A transient storage of the 59Fe-label in fat tissue was observed only from oral ferrocene but not from TMH-ferrocene. Due to the outstandingly high bioavailability of TMH-ferrocene, the chronic feeding of this compound resulted in a fast and progressive iron overload in rats (liver iron: 16.9 mg Fe/g wet weight after 10 weeks of feeding a diet containing 0.5% TMH-ferrocene), and can be regarded as the best characterized and most useful animal model for severe hepatocellular iron overload in humans.

Animals↗
PubMed1995

Brain iron in the ferrocene-loaded rat: its chelation and influence on dopamine metabolism.

After administration of the ferrocene derivative 3,5,5-trimethyl hexanoyl ferrocene to rats for 4 weeks various brain regions including substantia nigra, cerebellum and cerebral cortex showed up to 50% increase in iron content. Subsequent administration of one of the hydroxypyridones CP20, CP24 and CP94, or the siderophore desferrioxamine caused a significant decrease in the iron content of these various brain regions. Each of the hydroxypyridones and the siderophore influenced dopamine metabolism by causing significant variations in both homovanillic acid and dopamine turnover.

Animals↗
PubMed1994

3,5,5-Trimethylhexanoylferrocene induction of heme oxygenase activity in normal hepatocytes.

Recent work showed that the combination of 50 microM glutethimide plus 50 microM ferric nitrilotriacetate (FeNTA) synergistically induces heme oxygenase (HO) activity in cultured chick embryo liver cells (Cable et al., Biochem Biophys Res Commun 168: 176-181, 1990). This synergistic induction is due to increased heme synthesis, which then acts to increase HO gene transcription. The aim of the current studies was to characterize the effects on hepatic heme metabolism of (3,5,5-trimethylhexanoyl)ferrocene (TMH-ferrocene), which causes hepatic iron-loading in rats. Unlike FeNTA, TMH-ferrocene alone maximally induced HO activity at 5-10 microM TMH-ferrocene. At higher concentrations, HO activities declined, as did total cellular protein synthesis. Induction of HO was maximal after a 12-hr exposure to TMH-ferrocene, similar to induction by glutethimide plus FeNTA. The effect of TMH-ferrocene on HO could not be ascribed to greater cellular uptake of iron, since cell-associated iron levels were higher after FeNTA than after TMH-ferrocene treatment. TMH-ferrocene (up to 20 microM) did not induce delta-aminolevulinic acid synthase activity. Uroporphyrin accumulation in cells treated with TMH-ferrocene was minimal, but the combination of TMH-ferrocene and glutethimide caused a synergistic increase in uroporphyrin accumulation, similar to treatment with glutethimide plus FeNTA. 4,6-Dioxoheptanoic acid, an inhibitor of heme synthesis, blocked the induction of HO caused by glutethimide and FeNTA, but did not decrease the induction of HO by TMH-ferrocene. TMH-ferrocene-mediated induction of HO does not appear to be due to lipid peroxidation, since malondialdehyde formation was greater for ferrocene (a structural analog of TMH-ferrocene that does not induce HO) than for TMH-ferrocene. Furthermore, the anti-oxidant, butylated hydroxyanisole, which prevented lipid peroxidation, decreased HO induced by glutethimide plus FeNTA, but butylated hydroxyanisole did not affect HO induced by TMH-ferrocene. We conclude that, unlike the combination of glutethimide plus FeNTA, TMH-ferrocene induces HO activity by a mechanism that is independent of cellular heme synthesis.

Animals↗
PubMed1996

N-(2-ferrocene-ethyl)maleimide: a new electroactive sulphydryl-specific reagent for cysteine-containing peptides and proteins.

We report the synthesis and application of a specific electroactive label, N-(2-ferrocene-ethyl)maleimide, which provides new redox properties to organic compounds and proteins possessing sulphydryl groups. Its reaction conditions with the cysteine-containing peptide, glutathione, and a terminal monooxygenase enzyme, cytochrome P450cam are presented. The labelled peptide and enzyme acquired reversible electrochemical properties due to the attached ferrocene moiety.

Bacillus cereus↗
PubMed1993

Non-transferrin-bound-iron in serum and low-molecular-weight-iron in the liver of dietary iron-loaded rats.

1. The feeding of 0.5% (3,5,5-trimethylhexanoyl)ferrocene (TMH-ferrocene) in rats resulted in a severe and progressive liver siderosis (total liver iron, 30 mg/g liver wet weight, after 30 weeks). 2. High concentrations of an iron-rich ferritin (up to 250 mg/l) were detected in serum of heavily iron-loaded rats forming a large fraction of non-transferrin-bound-iron (5000 micrograms/dl in maximum). 3. Ferritin and not haemosiderin was the major iron storage protein in the liver. 4. The total liver iron concentration (from 0.4 to > 30 mg Fe/g wet wt) but not the cytosolic low-molecular-weight-iron fraction (from 0.5 to 2.5 microM) was extremely increased during iron-loading.

Animals↗
PubMed1992

Electrochemical enzyme immunoassay for detection of toxic substances.

Sensors that provide reliable, rapid measurement of toxic substances are needed to solve significant human health and safety problems. We developed a new biosensor design that combines the advantages of immunoassay with electrochemical response. We established that this enzyme-linked immunosensor measures toxic substances in biological samples. The biosensor consists of two major elements: (1) an electrical conducting layer having immobilized enzyme, polyclonal or monoclonal antibodies, and other necessary reagents, and (2) the electronic components used in the signal readout. The result is an amperometric immunoassay based on coupling the immunochemical reaction to the enzyme electrode response by using a soluble, electrochemically active mediator. The specific question addressed was: Does the system's immunochemical detection reliably respond at sufficiently low analyte concentrations? We present our results in these areas: (1) enzyme immobilization on colloidal gold; (2) colloidal gold-enzyme deposition on the electrode surface; (3) mediator-antigen conjugate synthesis; (4) antibody incorporation at the electrode surface; (5) bioelectrode characterization and optimization; and (6) immunosensor demonstration to detect antigen. Sensors that employ immunochemical detection will have broad applicability to detect/diagnose toxic substances in biological samples such as blood and urine and in environmental samples such as wastewater and drinking water.

Biosensing Techniques↗
PubMed1986

Potentially-implantable, ferrocene-mediated glucose sensor.

We describe the construction and in vitro testing of a new potentially-implantable amperometric glucose sensor which is based on mediated electron transfer between immobilized glucose oxidase and a graphite base electrode. Under potentiostatic control, entrapped 1,1'-dimethylferrocene acts as an alternative electron acceptor to oxygen and provides a sensing strategy which is relatively unaffected by possible fluctuations in in vivo oxygen tension. Simple 1 mm wide electrodes with a polyurethane membrane gave linear current responses to at least 20 mmol/l glucose with a mean response time of 68 s. An acceptable proportion (17%) of electrodes had low or zero drift over 17 h at 37 degrees C. With plasma samples from diabetic and non-diabetic subjects, glucose concentrations measured by the sensor were significantly correlated with values obtained by a reference laboratory glucose analyser but were proportionally lower. Extension of this study to in vivo testing and further miniaturization of electrodes is justified.

Blood Glucose↗