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PubMed2005

Induction of hepatic metallothionein by trivalent cerium: role of interleukin 6.

Metallothionein (MT) is a small sulfydryl-rich protein that binds to and is inducible by heavy metals such as mercury, cadmium, zinc, and copper. However, little is known about the induction of MT by trivalent metals except for bismuth. In this study, we examined the induction of MT synthesis by cerium, a trivalent lanthanoid metal. Administration of cerium chloride (CeCl3) to mice resulted in accumulation of cerium and induction of MT in the liver in a dose-dependent manner. Distribution profiles of metals in the soluble fraction of the liver of CeCl3-treated mice analyzed by high performance liquid chromatography/inductively coupled argon plasma-mass spectrometry (HPLC/ICP-MS) demonstrated that the metal bound to MT-I and MT-II was zinc, but not cerium. Administration of CeCl3 caused increases in the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the levels of serum amyloid A (SAA), an acute phase protein. Among inflammatory cytokines examined, interleukin 6 (IL-6) exhibited a marked increase in the serum at 3 h after the CeCl3 administration. In order to evaluate the involvement of IL-6 in the induction of MT by cerium, we examined MT induction by CeCl3 in IL-6 null mice. Both the induction of hepatic MT and the increases in SAA levels were markedly suppressed in IL-6 null mice. These results suggest that IL-6 plays an important role in the induction of hepatic MT by cerium.

Animals↗
PubMed2006

Cerium depresses endocardial endothelial cell-mediated proliferation of cardiac fibroblasts.

Cerium has been implicated in the pathogenesis of cardiac disorders such as acute myocardial infarction and endomyocardial fibrosis (EMF). A geochemical hypothesis for the causation of EMF linked the cardiac lesions to magnesium deficiency consequent to malnutrition and increased cardiac levels of cerium derived from monazite soils in the coastal regions of the tropics. We tested the hypothesis that the stimulus for fibroblast proliferation and enhanced collagen synthesis in EMF is derived from cardiac endothelial cells activated or injured by cerium. We explored whether endocardial endothelial cells exposed to cerium secrete factors responsible for the increased proliferation and collagen synthesis in cardiac fibroblasts. Our results suggest that the growth response of cardiac fibroblasts to cerium is not mediated through growth factors secreted by endocardial endothelium and that the cardiac lesions in EMF result from direct stimulation of subendocardial fibroblasts by cerium.

Animals↗
PubMed1984

A new cerium-based method for cytochemical localization of thiamine pyrophosphatase in the Golgi complex of rat hepatocytes. Comparison with the lead technique.

The use of cerium chloride for the localization of thiamine-pyrophosphatase (TPPase) in rat liver parenchymal cells has been investigated and the results are compared with the classical lead capture method. A medium containing 3 mM cerium chloride gave the most uniform and consistent results with a homogeneous electron dense reaction product in the first trans lamella of the Golgi complex and a weak staining of endoplasmic reticulum. The fine deposits of cerium phosphate filled completely the first trans Golgi cisterna. In contrast the reaction product of the lead-based method appeared clumpy and aggregated with an irregular distribution over both Golgi complex and endoplasmic reticulum. Higher and lower concentrations of cerium chloride than 3 mM gave inconsistent results. The present study demonstrates that the cerium-based method is superior to the classical lead-technique for the localization of TPPase.

Animals↗
PubMed1992

Effect of cerium nitrate-silver sulphadiazine on deep dermal burns: a histological hypothesis.

Although there are excellent clinical results from using cerium nitrate plus silver sulphadiazine in the treatment of deep dermal burns in our burn centre, its mechanism of action remains unexplained. We set up a prospective study to establish a hypothesis which could explain the formation of the typical leathery crust. Burns treated with cerium nitrate plus silver sulphadiazine and silver sulphadiazine alone were compared histologically and metallurgically. Application of cerium nitrate plus silver sulphadiazine on deep dermal burns caused superficial connective tissue calcification with few deep dermal changes. Cerium penetration was low and silver was never detected intradermally. The precipitation of cerium and pyrophosphate destroys the calcification inhibitory function of the latter, creates multiple calcification nuclei and leads to superficial dermal calcification. No calcium was detectable in biopsies from silver sulphadiazine-treated wounds. No major toxicological side-effects were seen during this study. The clinical results were favourable, as have been reported previously.

Adolescent↗
PubMed2000

Effects of cerium nitrate bathing and prompt burn wound excision on IL-6 and TNF-alpha levels in burned rats.

The physiopathological events following thermal injury are not limited to the surface effects of heat but are also related to acute inflammatory reactions. Both tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are important mediators of the acute and severe inflammatory reaction in thermal injury. Surgical manipulation of the burn wound is known to prevent excessive release of cytokines. Cerium nitrate--a rare earth element--has been reported to have a protective effect against postburn immunosuppression. The aim of this study was to compare the effects of burn wound debridement and treatment with cerium nitrate bathing on the serum levels of TNF-alpha and IL-6 in rats. Treatment by cerium nitrate bathing prevented the elevation of TNF-alpha levels in the early period after thermal injury. The experimental study showed, as in other studies, that high levels of IL-6 appear to inhibit TNF-alpha elevation. High levels of IL-6 and, as a result, relatively low levels of TNF-alpha in the early period of thermal injury may limit the severity of the inflammatory reaction, which is caused by TNF, the most potent inflammatory cytokine. Since similar levels of IL-6 and TNF-alpha were achieved by both cerium nitrate bathing and burn wound debridement, cerium nitrate may be considered as equivalent to prompt excision of burn eschar.

Animals↗
PubMed1997

Cerium-based ultracytochemical localization of aspartate transcarbamylase activity in the cell membrane complex of Saccharomyces cerevisiae.

Aspartate transcarbamylase (ATCase) activity was localized ultracytochemically in the yeast Saccharomyces cerevisiae by precipitation of its reaction product orthophosphate as cerium phosphate. We prefixed yeast cells with ice-cold 1% glutaraldehyde for 30 min which preserved 80% of ATCase activity. Cells were washed and incubated with ATCase substrates (aspartate, carbamyl phosphate) plus cerium chloride, and postfixed by osmium tetroxide. In cells from exponential batch cultures, deposits of cerium phosphate delineated simultaneously or alternatively membranes of the secretory pathway: nuclear envelope, endoplasmic reticulum, Golgi complex and the plasmalemma; mitochondrial membranes and intramitochondrial fibrous component were labelled as well. Deposits of cerium phosphate were never observed in the nucleoplasm. Cells incubated in the absence of cerium or ATCase substrates and mutant S. cerevisiae cells lacking ATCase activity served as controls. Small round electron-dense condensates were found to be randomly distributed within some cells, both in control and experimental runs, in the nucleoplasm, cytoplasm and mitochondrial matrix and represented undefined osmicated endogenous compounds. Our results suggest that the synthesis of pyrimidine precursors occurs in membranes, where compounds such as UDP-glucose and CDP-diglycerides are needed for membrane and/or yeast cell wall synthesis. The possible contribution of ATCase activity found in the nuclear envelope to nucleic acid synthesis remains to be clarified.

Aspartate Carbamoyltransferase↗
PubMed2002

Induction of early bolting in Arabidopsis thaliana by triacontanol, cerium and lanthanum is correlated with increased endogenous concentration of isopentenyl adenosine (iPAdos).

The effects of triacontanol (TRIA), applied singly or in combination with cerium nitrate and lanthanum nitrate, on bolting of Arabidopsis thaliana were studied. Triacontanol (0.1 to 0.6 microM) added to the culture medium induced early bolting. TRIA (0.3 microM) applied with low concentrations of cerium and lanthanum caused a synergistic stimulation of bolting. In medium containing 0.3 microM TRIA, 0.1 microM cerium nitrate and 0.1 mM lanthanum nitrate, 82% of the plants bolted 20 d after seed sowing compared to only 8.6% in basal medium and 47.8% in medium with TRIA only. The changes in the endogenous concentrations of total cytokinins of the isopentenyl adenine (IP) subfamily in the leaf and root tissues were correlated with TRIA-induced early bolting. The combined treatment of TRIA (0.3 microM), cerium nitrate (0.1 microM) and lanthanum nitrate (0.1 mM) resulted in a significant increase in the endogenous concentrations of total cytokinins of the IP subfamily in the root and leaf tissues compared to plants growing in the basal medium and medium with TRIA. The exogenous application of six natural cytokinins to the plants revealed that only isopentenyl adenosine (iPAdos) was as effective as TRIA on floral bud formation. iPAdos was also found to have similar effects as TRIA on root growth and reproductive growth. These results suggest a correlation between the early bolting induced by TRIA, cerium and lanthanum and the production of higher concentrations of endogenous iPAdos.

Adenine↗
PubMed1981

A prospective analysis of silver sulfadiazine with and without cerium nitrate as a topical agent in the treatment of severely burned children.

Previous studies have indicated that combining cerium nitrate with silver sulfadiazine (Silvadene, Marion Labs) yields a superior topical agent for the treatment of burns. Cerium nitrate in silver sulfadiazine was tested in a controlled study with silver sulfadiazine alone. The study population consisted of two groups of children suffering burns greater than 30% of the body surface. The patients ranged in size from 1 to 21 years. The study period was for the first 10 weeks of hospitalization. Quantitative surface cultures were used to monitor burn wound flora. No superiority for the silver sulfadiazine-cerium nitrate combination was demonstrated. In fact, cultures indicate a significantly greater percentage of Gram-negative pathogens in patients treated with the cerium mixture. Cerium nitrate could possibly prove of greatest benefit if used as a reserve therapy for colonizing organisms which do not routinely respond to silver sulfadiazine.

Administration, Topical↗
PubMed1999

Cerium-based histochemical demonstration of oxidative stress in taurocholate-induced acute pancreatitis in rats. A confocal laser scanning microscopic study.

Direct in vivo histological detection of oxygen-derived free radicals (OFRs) in inflammatory conditions is not fully resolved. We report an application of cerium histochemistry (in which capture of OFRs by Ce atoms results in laser-reflectant cerium-perhydroxide precipitates) combined with reflectance confocal laser scanning microscopy (CLSM) to demonstrate the evolution of oxidative stress in taurocholate-induced acute pancreatitis (AP) in rats. Animals were perfused with CeCl(3) in vivo and cryostat sections of pancreata were studied by CLSM. Vascular endothelium was immunolabeled for PECAM-1. OFR production by isolated polymorphonuclear leukocytes (PMNs) incubated in vitro with CeCl(3) was quantified by image analysis. In the pancreas, strong OFR-derived cerium reflectance signals were seen in acinar cells at 1-2 hr, capillaries and small venules were frequently engorged by cerium precipitates, and adherent PMNs presented weak intracellular reflectance signals. At 8-24 hr, acinar cell OFR production decreased, whereas adherent/transmigrated PMNs displayed abundant intra- and pericellular reflectance. PECAM-1 expression was unchanged. PMNs from ascites or blood showed significant (p<0.01) time-dependent OFR production, plateauing from 2 hr. The modified cerium capture/CLSM method allows the co-demonstration of in vivo oxidative stress and cellular structures labeled with fluorescent markers. In vivo oxidative stress was shown histologically for the first time in experimental AP.

Acute Disease↗
PubMed1990

Quantitative histochemical analysis of glucose-6-phosphatase activity in rat liver using an optimized cerium-diaminobenzidine method.

We have optimized a cerium-diaminobenzidine-based method for histochemical analysis of glucose-6-phosphatase (G6Pase) activity and have determined quantitative data on the zonal distribution pattern in the liver acinus of fasted male rats. In the cerium-diaminobenzidine technique, cerium instead of lead ions is used as capturing reagent for the enzymatically liberated phosphate. For light microscopy, the primary reaction product, cerium phosphate, is then visualized by conversion into cerium perhydroxide using hydrogen peroxide and subsequent oxidative polymerization of diaminobenzidine to diaminobenzidine brown as the final reaction product. Variation of the substrate (glucose-6-phosphate) concentration in the incubation medium yielded in periportal zones a KM value of 2.3 +/- 0.7 mM and a Vmax value of 0.96 +/- 0.18 (expressed as mean integrated absorbance). In perivenous zones a KM value of 1.1 +/- 0.4 mM and a Vmax value of 0.51 +/- 0.08 were calculated. The cytophotometric analysis performed in this study demonstrated for the first time that a functional difference of G6Pase, the key enzyme for gluconeogenesis, exists in the periportal and perivenous zones of the liver acinus. Periportal zones contain twice as many enzyme molecules (high Vmax) as perivenous zones, but the affinity for the substrate is twice as low. This may have important implications for the concept of metabolic zonation of the liver and also for glucose homeostasis in the blood.

3,3'-Diaminobenzidine↗
PubMed2000

Bacteriostatic effects of cerium-humic acid complex: an experimental study.

The bacteriostatic potency of the cerium-humic acid complex was evaluated by experimental measurement of this complex interaction with E. coli, Bacillus pyocyaneus, Staphylococcus aureus, Leuconostoc and Streptococcus faecalis, and by comparison bacteriostatic effects with the cerium-citrate complex. The experimental results indicated that the cerium-humic acid complex strongly inhibited growth of all five bacterial strains, and its diameter of bacteriostatic circles were more than 30 mm. The minimal bacteria-inhibiting concentration were 1 x 10(-3), 2 x 10(-3) and 1 x 10(-2) mol/L for E. coli and Bacillus pyocyaneus, Staphylococcus aureus, and Leuconostoc and Streptococcus faecalis individually, and the measured minimal bactericidal concentrations were 2 x 10(-3) and 1 x 10(-2) mol/L for Bacillus pyocyaneus, E. coli, and Leuconostoc. To kill Staphylococcus aureus and Streptococcus faecalis, the concentration had to be more than 1 x 10(-20 mol/L. On the contrary, we found that cerium-citrate complex did not inhibit the growth of the above five bacteria, but stimulated bacterial growth. The completely different bacteriostatic results of two cerium complexes may hint that the association and chemical properties of the two complexes were different.

Anti-Bacterial Agents↗
PubMed1980

In vivo and in vitro antimicrobial activity of silver sulfadiazine and cerium nitrate.

The antimicrobial activity of cerium nitrate and silver sulfadiazine was assessed in vitro and in vivo using Pseudomonas aeruginosa. In vitro, the activity of silver sulfadiazine was significantly greater than that of cerium nitrate. Synergism between silver sulfadiazine and cerium nitrate was observed in water or saline solution suspensions, but not in broth. In vivo, cerium nitrate offered no therapeutic benefit in reducing wound infection in contaminated wounds. Treatment of similar wounds with silver sulfadiazine resulted in a significant decrease in wound infection and in the level of viable bacteria when compared with that for untreated controls. The addition of cerium nitrate to silver sulfadiazine in aqueous soultion reduced the therapeutic benefit of silver sulfadiazine.

Animals↗
PubMed1977

Topical chemotherapy for burns using cerium salts and silver sulfadiazine.

These experimental data indicate that cerium compounds exert a measurable antimicrobial action in vitro. In vivo the simultaneous use of cerium sulfadiazine and silver sulfadiazine was more effective than silver sulfadiazine alone or the combination of cerous nitrate and silver sulfadiazine. When cerous nitrate was used clically, gram-positive bacteria predominated. In contrast, wounds exposed to silver salts alone harbor a predominately gram-negative flora. The combination of cerous nitrate and silver sulfadiazine appears to provide a broad spectrum inhibitory to both types of organisms. It is apparent that a sampling problem exists in any attempt to monitor wounds that may exceed a square meter in extent. These bacteriologic data pertain only to the surface flora. The need to culture tissue samples of burn wounds has been emphasized. Our experience, however, is that invasion of deep tissue without dense surface colonization, greater than 10(5), is infrequent. Furthermore, fragments of eschar were submitted regularly for culture; those results confirmed the surface culture findins. The characteristic yellow-green color of cerium nitrate treated eschars may results from oxidation of trivalent cerium to yellow ceric ions. Free silver and sulfadiazine ions are available also in small amounts because of limited ionization of the highly insoluble silver sulfadiazine. This might promote the in vivo formation of cerous sulfadiazine and would provide a continuous source of ionic cerium for microbial inhibition. The modification of silver sulfadiazine cream by incorporating cerous nitrate into it strikingly enhances its topical antiseptic effect in burn wounds without increasing toxicity.

Administration, Topical↗
PubMed1996

Spectrofluorometric trace determination of cerium(III) in sodium hexametaphosphate solutions.

The use of sodium hexametaphosphate in the spectrofluorometric determination of trace amounts of cerium(III) ions is described. Sodium hexametaphosphate acts as a specific reagent for enhancing the fluorescence intensity of cerium(III) in aqueous solutions. The apparent excitation and fluorescence wavelength used are 304 and 344 nm, respectively. Maximum fluorescence intensity is obtained by irradiating Ce(III) dissolved in 5.346 g/l sodium hexametaphosphate solution at room temperature. The fluorescence varies linearly with the concentration of cerium(III) in the range of 0.001-60 microg/ml. The coefficient of variation for 45 microg/ml Ce(III) in 5.346 g/l sodium hexametaphosphate solution is 1. The quenching effects of other lanthanides and some inorganic anions are given. This technique permits a direct and rapid determination of cerium(III) in rare earth mixtures and cerium concentrates.

Journal Article↗
PubMed2005

Experimental determination of water activity for binary aqueous cerium(III) ionic solutions: application to an assessment of the predictive capability of the binding mean spherical approximation model.

This work is aimed at a description of the thermodynamic properties of actinide salt solutions at high concentration. The predictive capability of the binding mean spherical approximation (BIMSA) theory to describe the thermodynamic properties of electrolytes is assessed in the case of aqueous solutions of lanthanide(III) nitrate and chloride salts. Osmotic coefficients of cerium(III) nitrate and chloride were calculated from other lanthanide(III) salts properties. In parallel, concentrated binary solutions of cerium nitrate were prepared in order to measure experimentally its water activity and density as a function of concentration, at 25 degrees C. Water activities of several binary solutions of cerium chloride were also measured to check existing data on this salt. Then, the properties of cerium chloride and cerium nitrate solutions were compared within the BIMSA model. Osmotic coefficient values for promethium nitrate and promethium chloride given by this theory are proposed. Finally, water activity measurements were made to examine the fact that the ternary system Ce(NO3)3/HNO3/H2O and the quaternary system Ce(NO3)3/HNO3/N2H5NO3/H2O may be regarded as "simple solutions" (in the sense of Zdanovskii and Mikulin).

Journal Article↗
PubMed2005

Precipitation-redispersion of cerium oxide nanoparticles with poly(acrylic acid): toward stable dispersions.

We exploit a precipitation-redispersion mechanism for complexation of short chain polyelectrolytes with cerium oxide nanoparticles to extend their stability ranges. As synthesized, cerium oxide sols at pH 1.4 consist of monodisperse cationic nanocrystalline particles having a hydrodynamic diameter of 10 nm and a molecular weight of 400 000 g mol(-1). We show that short chain uncharged poly(acrylic acid) at low pH when added to a cerium oxide sols leads to macroscopic precipitation. As the pH is increased, the solution spontaneously redisperses into a clear solution of single particles with an anionic poly(acrylic acid) corona. The structure and dynamics of cerium oxide nanosols and their hybrid polymer-inorganic complexes in solution are investigated by static and dynamic light scattering, X-ray scattering, and chemical analysis. Quantitative analysis of the redispersed sol gives rise to an estimate of 40-50 polymer chains per particle for stable suspension. This amount represents 20% of the mass of the polymer-nanoparticle complexes. This complexation adds utility to the otherwise unstable cerium oxide dispersions by extending the range of stability of the sols in terms of pH, ionic strength, and concentration.

Journal Article↗
PubMed1995

Localization of Hydrogen Peroxide Production in Pisum sativum L. Using Epi-Polarization Microscopy to Follow Cerium Perhydroxide Deposition.

Cerium is becoming an increasingly popular reagent for histochemical localization of oxidases and phosphatases because it combines directly with reaction products to form fine precipitates of electron-dense materials that can be easily detected using transmission electron microscopy or laser confocal scanning microscopy. We used epi-polarization microscopy to detect cerium perhydroxide deposits formed when H2O2 was produced by diamine oxidase in pea (Pisum sativum L.) epicotyls exposed to exogenous putrescine. Diamine oxidase activity was abundant in cortical cell walls but showed little, if any, association with vascular tissues. Maps of cerium deposition generated using scanning electron microscopy/x-ray microanalysis verified these observations. This study demonstrates the use of epi-polarization microscopy to follow cerium deposition, and the ready accessibility of this microscopy technique should facilitate more widespread use of cerium for plant histochemistry and cytochemistry.

Journal Article↗
PubMed2002

Spectrophotometric determination of cerium(IV) using a phenothiazine derivative.

A simple, rapid and sensitive spectrophotometric method has been proposed for the determination of cerium(IV) using a phenothiazine derivative, propionyl promazine phosphate (PPP). This method is based on the formation of a red-colored radical cation upon a reaction of PPP with cerium(IV) in a phosphoric acid medium having maximum absorbance at 513 nm. Beer's law is valid over the concentration range of 1-11 microg/ml with a Sandell's sensitivity value of 16.14 ng/cm2. The proposed method has been successfully applied to the analysis of magnesium-base cerium alloys and synthetic mixtures corresponding to various cerium alloys. Other phenothiazine derivatives viz. butaperazine dimaleate and propericiazine were also used for the determination of cerium(IV).

Journal Article↗