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PubMed2006

Chromium(III) complexes of D-glucosaminic acid and their effect on decreasing blood sugar in vivo.

Two chromium(III) complexes of glucosaminic acid were synthesized by neutralization and exchange reaction. The formation of 1 : 1 and 2 : 3 (Cr : glucosaminate) complexes was confirmed by elemental analyses and spectroscopic studies. The effect of the complexes on decreasing blood sugar was investigated on type-2 diabetes model rats induced by tetraoxypyrimidine. The results indicated that the effect on decreasing blood sugar was comparable to that of picolinate chromium complex (Cr(pic)(3)) currently used world wide.

Alloxan↗
PubMed2006

Enhanced cardiovascular function and energy level by a novel chromium (III)-supplement.

The impetus for the novel Energy Formula (EF) which combines the niacin-bound chromium (III) (0.45%) (NBC), standardized extract of Withania somnifera extracts (10.71%), caffeine (22.76%), D-ribose (10.71%) and selected amino acids such as phenylalanine, taurine and glutamine (55.37%) was based on the knowledge of the cardioprotective potentials of the Withania somnifera extract, caffeine and D-ribose as well as their abilities to increase energy levels and the abilities of amino acids to increase the muscle mass and energy levels. The effect of oral supplementation of EF on the safety, myocardial energy levels and cardioprotective ability were investigated in an ischemic-reperfused myocardium model in both male and female Sprague-Dawley rats over 90 days trial period. At the completion of 90 days, the EF-treated male and female rats gained 9.4% and 3.1% less body weights, respectively, as compared to their corresponding control groups. No significant difference was found in the levels of lipid peroxidation and activities of hepatic Aspartate transaminase, Alanine transaminase and Alkaline phosphatase in EF treatment when compared with control animals. The male and female rat hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion at 30 and 90 days of EF treatment. Cardiovascular functions including heart rate, coronary flow, aortic flow, dp/dt(max), left ventricular developed pressure (LVDP) and infarct size were monitored. The levels of myocardial adenosine triphosphate (ATP), creatine phosphate (CP), phospho-adenosine monophosphate kinase (p-AMPK) levels, were analyzed at the end of 30 and 90 days of treatment. Significant improvement was observed in all parameters in the EF treatment groups as compared to their corresponding controls. Thus the niacin-bound chromium (III) based energy formula is safe and effective supplement to boost energy levels and cardioprotection.

Adenosine Monophosphate↗
PubMed1976

Intestinal blood loss after a new anti-inflammatory drug, sulindac.

Sulindac was tested for fecal blood loss in 40 healthy male subjects whose red cells had been labeled with Na2 51 CrO4. Two daily dose levels of 240 mg and 400 mg were compared with 4.8 gm of aspirin and placebo for 2 wk. At day 15, aspirin-induced blood loss was greater than that of both dose levels of sulindac and of placebo (p less than 0.05). There were no significant differences between the two sulindac groups and the placebo group. Aspirin caused more adverse reactions than sulindac, 240 mg (p less than 0.05), 400 mg (p less than 0.05), and placebo (p less than 0.05).

Adult↗
PubMedDate not supplied

Effects of trivalent chromium on hepatic CYP-linked monooxygenases in laying hens.

Chromium is an essential nutrient required for the metabolism of carbohydrates and lipids in humans and many animal species. We evaluated whether feeding laying hens with high levels of different chemical forms of trivalent chromium may affect hepatic metabolizing cytochrome P-450 (CYP)-linked enzymes. Modulation of CYP-dependent monooxygenases (which play a pivotal role in the endogenous metabolism) by Cr(III) was tested using either specific substrates as probes of different CYPs or testosterone as a multi-bioprobe. The CYP-supported oxidases were studied in liver microsomes from laying hens fed with diet supplemented with either 25 or 50 ppm chromium chloride as a yeast or as aminoniacinate. Although at 25 ppm no appreciable effects were observed, at 50 ppm a general inactivation of the recorded monooxygenases (ranging from 34% loss for ethoxycoumarin O-deethylase with chromium chloride to 85% loss for O-deethylation of ethoxyresorufin with either chromium yeast or aminoniacinate) were achieved in the supplemented groups vs controls. The only exception was the O-dealkylation of pentoxyresorufin, which was significantly boosted by both chromium yeast (up to 65% increase) and chromium aminoniacinate (up to 141%). Measurements of the regio- and stereoselective hydroxylation of testosterone used as a multi-bioprobe corroborated the inactivating properties of Cr(III) at the higher dose. Taken as a whole, these findings seem to indicate that high levels of Cr(III) supplementation can substantially impair CYP-catalysed drug metabolism in laying hens.

Animals↗
PubMed1995

Chromium-induced production of reactive oxygen species, DNA single-strand breaks, nitric oxide production, and lactate dehydrogenase leakage in J774A.1 cell cultures.

The involvement of oxidative stress in the toxicity of chromium (VI) and chromium (III) has been proposed. We have therefore examined the effects of these cations on the production of superoxide anion, nitric oxide (NO), and DNA single strand breaks (SSB) in J774A.1 macrophage cells in culture as well as the effects on lactate dehydrogenase (LDH) leakage and cell viability. Following a 48 hour incubation, over twofold increases in superoxide anion and NO production were observed at concentrations of approximately 0.30 and 50 microM for Cr (VI) and Cr (III), respectively. The patterns of cell viability and LDH leakage paralleled superoxide anion and NO production for Cr (VI) and Cr (III). A 50% decrease in viability was observed at approximately the concentrations that produced a twofold increase in superoxide and NO production. Concentration-dependent increases in DNA-SSB were observed after incubation with Cr (III) with maximum increases occurring at a concentration of approximately 60 microM. Cr (VI) had no effect on the incidence of DNA-SSB at any of the tested concentrations. The results indicate that Cr (VI) and Cr (III) are toxic to the J774A.1 cell line, and the toxicity may be due at least in part to an oxidative stress induced by the production of reactive oxygen species.

Cell Line↗
PubMed1995

Long-term exposure to chromium(VI) oxide leads to defects in sulfate transport system in Chinese hamster ovary cells.

Chromium(VI) resistant Chinese hamster ovary (CHO) cell lines were established in this study by exposing parental CHO-K1 cells to sequential increases in CrO3 concentration. The final concentration of CrO3 used for selection was 7 microM for Cr7 and 16 microM for Cr16 cells. Cr16-1 was a subclone derived from Cr16 cells. Next, these resistant cells were cultured in media without CrO3 for more than 6 months. The resistance of these cells to CrO3 was determined by colony-forming ability following a 24-h treatment. The LD50 of CrO3 for chromium(VI) resistant cells was at least 25-fold higher than that of the parental cells. The cellular growth rate, chromosome number, and the hprt mutation frequency of these chromium(VI) resistant cells were quite similar to their parental cells. The glutathione level, glutathione S-transferase, catalase activity, and metallothionine mRNA level in Cr7 and Cr16-1 cells were not significantly different from their parental cells. Furthermore, Cr16-1 cells were as sensitive as CHO-K1 cells to free-radical generating agents, including hydrogen peroxide, nickel chloride, and methanesulfonate methyl ester, and emetine, i.e., a protein synthesis inhibitor. The uptake of chromium(VI) and the remaining amount of this metal in these resistant and the parental cell lines were assayed by atomic absorption spectrophotometry. Experimental results indicated that a vastly smaller amount of CrO3 entered the resistant cell lines than their parental cells did. A comparison was made of the sulfate uptake abilities of CHO-K1 and chromium(VI) resistant cell lines. These results revealed that the uptake of sulfate anion was substantially reduced in Cr7 and Cr16-1 cells. Extracellular chloride reduced sulfate uptake in CHO-K1 but not in Cr16-1 cells. Therefore, the major causative for chromium(VI) resistance in these resistant cells could possibly be due to the defects in SO4(2-)/C1- transport system for uptake chromium(VI).

Animals↗
PubMed2006

Methane activation by chromium oxide cations in the gas phase: a theoretical study.

Density Functional Theory, in its B3LYP formulation, was used to explore quantitative details of the potential energy hypersurfaces for the C-H bond activation reaction of methane by chromium dioxide cation. Both doublet ground and quartet excited states of the cation were considered, and all the minima and transition states localized along the paths leading to the formation of the experimentally observed products were characterized. All the calculated paths involve spin inversions that decrease the barrier heights of the involved transition states but do not play a significant role. Reaction pathways were also studied employing the nonhybrid BP86 functional, the reparametrized B3LYP* functional, and the CCSD(T) approach. Because other examples in the literature indicate that sequential ligation enhances the reactivity of bare transition metals cations, the state-selective reactivity of the chromium monoxide cation with respect to methane was also investigated and compared with that of the bare cation.

Cations↗
PubMed2004

Epigenetic and gene expression changes related to transgenerational carcinogenesis.

Transgenerational carcinogenesis refers to transmission of cancer risk to the untreated progeny of parents exposed to carcinogens before mating. Accumulated evidence suggests that the mechanism of this process is epigenetic, and might involve hormonal and gene expression changes in offspring. To begin to test this hypothesis, we utilized a mouse model (NIH Swiss) in which exposure of fathers to Cr(III) chloride 2 wk before mating can alter incidence of neoplastic and nonneoplastic changes in offspring tissues. Utilizing a MS-RDA approach, we found that the sperm of these fathers had a significantly higher percentage of undermethylated copies of the 45S ribosomal RNA gene (rRNA); this finding was confirmed by bisulfite sequencing. Because gene methylation is a known mechanism of expression control in germ cells, and ribosomal RNA levels have been linked to cancer, these findings are consistent with the hypothesis. Secondly, we observed that offspring of Cr(III)-treated fathers were significantly heavier than controls, and had higher levels of serum T3. Possible effects of T3 levels on gene expression in the offspring were examined by microarray analysis of cDNAs from liver. A total of 58 genes, including 25 named genes, had expression ratios that correlated significantly with serum T3 ratios at P </= 0.001. Some of these genes have potential roles in growth and/or tumor suppression. These results also support the hypothesis of an epigenetic and/or gene expression-based mechanism for transgenerational carcinogenesis. Published 2004 Wiley-Liss, Inc.

Animals↗
PubMed2004

Thermodynamic study of some chromium-containing gaseous molecules by high-temperature mass spectrometry.

A number of gaseous oxyacid salts have been identified by Knudsen effusion mass spectrometry, while vaporizing Cr(2)O(3) and mixtures of Cr(2)O(3)+Nb(2)O(5), Cr(2)O(3)+Ta(2)O(5), Cr(2)O(3)+BaO, and Cr(2)O(3)+Mg(2)P(2)O(7) from molybdenum and tungsten cells. The stabilities of the gaseous molecules CrMoO(3), CrMoO(4), CrMoO(5), CrWO(3), CrWO(4), CrWO(5), CrNbO(3), CrTaO(3), CrPO(2), CrPO(3), BaCrO(2) and BaCrO(3) were deduced from the measurements. The thermodynamic properties of this gaseous chromium-containing species are summarized. Prediction is tentatively made of the stability of as-yet unstudied gaseous molecules.

Chromium Compounds↗
PubMedDate not supplied

Multiphoton confocal microscopy using a femtosecond Cr:forsterite laser.

With its output wavelength covering the infrared penetrating window of most biological tissues at 1,200-1,250 nm, the femtosecond Cr:forsterite laser shows high potential to serve as an excellent excitation source for the multiphoton fluorescence microscope. Its high output power, short optical pulse width, high stability, and low dispersion in fibers make it a perfect replacement for the currently widely used Ti:sapphire laser. In this paper, we study the capability of using a femtosecond Cr:forsterite laser in multiphoton scanning microscopy. We have performed the multiphoton excited photoluminescence spectrum measurement on several commonly used bioprobes using the 1,230 nm femtosecond pulses from a Cr:forsterite laser. Efficient fluorescence can be easily observed in these bioprobes through two-photon or three-photon excitation processes. These results will assist in the selection of dichroic beam splitter and band pass filters in a multiphoton microscopic system. We have also performed the autofluorescence spectrum measurement from chlorophylls in live leaves of the plant Arabidopsis thaliana excited by 1,230 nm femtosecond pulses from the Cr:forsterite laser. Bright luminescence from chlorophyll, centered at 673 and 728 nm, respectively, can be easily observed. Taking advantage of the bright two-photon photoluminescence from chlorophyll, we demonstrated the two-photon scanning paradermal and cross-sectional images of palisade mesophyll cells in live leaves of Arabidopsis thaliana.

Arabidopsis↗
PubMed1997

Isolation and characterization of a biologically active chromium oligopeptide from bovine liver.

Low-molecular-weight chromium-binding substance (LMWCr), the only known naturally occurring Cr-containing polypeptide from mammals and candidate for the biologically active form of chromium, has been isolated for the first time in yields sufficient for spectroscopic studies capable of providing structural and mechanistic data on a molecular level. The results of paramagnetic 1H NMR, electron paramagnetic resonance, and electronic spectroscopic studies indicate that the four chromic ions per polypeptide are probably arranged in an integer-spin tetranuclear assembly, although an alternate possibility, the presence of two dinuclear assemblies, could not be ruled out. This assembly (or assemblies) is bridged by anionic ligands and supported by carboxylates provided by the polypeptide.

Adipocytes↗
PubMed2000

DNA cleavage by a Chromium(III) complex.

A new Cr(III) complex with the empirical formula [Cr(Schiff base) (H(2)O)(2)]ClO(4), where the Schiff base is 2, 3-bis¿[(2-hydroxy-4-diethylamino) (phenyl) (methylene)]amino¿2-butenedinitrile has been synthesized and characterized spectroscopically. Binding of this complex to DNA has been studied using UV-visible spectroscopy. The complex has been found to bind to the major groove of DNA with a binding constant, K = (1.3 +/- 0.2) x 10(3) M(-1). The induced CD spectrum of the complex in the presence of DNA is also indicative of major groove binding. Gel electrophoresis of plasmid DNA in the presence of the complex shows that the complex brings about nicking of the DNA.

Chromium Compounds↗
PubMed2000

Cleavage of human orosomucoid by a chromium(V) species: relevance in biotoxicity of chromium.

A chromium(V) complex, CrO(salen)+, was generated in situ and its interaction with human orosomucoid (alpha1-acid glycoprotein) has been evaluated. The chromium(V) species has been found to oxidize the protein rapidly. A second order rate constant of 5 +/- 0.4 x 10(4) M(-1) s(-1) has been obtained for the redox process. Gel electrophoresis pattern of AGP in the presence of metal ion clearly reveals the decrease in the intensity of the AGP band with the subsequent formation of protein fragments of lower molecular weight. At higher metal ion concentration a continuous smear is observed which indicates the nonselective cleavage of the glycoprotein. Cleavage of AGP is through the direct pathway of oxidation by a highly reactive chromium(V) species.

Chromium Compounds↗
PubMed2001

Chromium(III)-induced structural changes and self-assembly of collagen.

Rat tail tendon (RTT) collagen has been reacted with a homologous series of chromium(III) complexes viz., (H2O)(4)Cr(OH)(2)Cr(H2O)(4+)(4) 1 (dimer), Cr(3)(OH)(4)(H2O)(5+)(9) 2 (trimer), and Cr(4)(OH)(4)(O2)(H2O)(4+)(12) 3 (tetramer), and the structural alterations brought about by these complexes have been investigated through atomic force microscopy (AFM) and circular dichroism (CD) studies. Examination of Cr(III)-treated tendons using AFM revealed changes in the D-periodicity of collagen, which may arise due to differences in the topological distribution of various Cr(III) complexes. Evidence for organisation of monomeric collagen into quarter staggered fibrils in the presence of Cr(III) dimer, 1, has been obtained. The quaternary structural changes induced by chromium in the protein have been correlated to the conformational changes of collagen in the absence of denaturation.

Acetic Acid↗
PubMed2001

Chromium(III)-mediated structural modification of glycoprotein: impact of the ligand and the oxidants.

The interaction of three types of chromium(III) complexes, [Cr(salen) (H2O2]+, [Cr(en)3]3+, and [Cr(EDTA) (H2O)]- with AGP has been investigated. [Cr(salen) (H2O2]+, [Cr(en)3]3+ and [Cr(EDTA) (H2O]- bind to Human alpha1-acid glycoprotein with a protein:metal ratio of 1:8, 1:6, and 1:4, respectively. The binding constant, K(b) was estimated to be 1.37 +/- 0.12 x 10(5) M(-1), 1.089 +/- 0.05 x 10(5) M(-1) and 5.3 +/- 0.05 x 10(4) M(-1) for [Cr(salen) (H2O2]+, [Cr(en)3]3+, and [Cr(EDTA) (H2O)]-, respectively. [Cr(en)3]3+ has been found to induce structural transition of AGP from the native twisted beta sheet to a more compact alpha-helix. The complexes, [Cr(salen) (H2O2]+ and [Cr(EDTA) (H2O]-, in the presence of H2O2, have been found to bring about nonspecific cleavage of AGP, whereas [Cr(en)3]3+ does not bring about any protein damage. Treatment of [Cr(salen) (H2O)2]+-protein adduct with iodosyl benzene on the other hand led to site specific cleavage of the protein. These results clearly demonstrate that protein damage brought about by chromium(III) complexes depends on the nature of the coordinated ligand, nature of the metal complex, and the nature of the oxidant.

Chromium Compounds↗
PubMed2001

Chromium chloride inhibits oxidative stress and TNF-alpha secretion caused by exposure to high glucose in cultured U937 monocytes.

Chromium supplementation has been proposed to promote the action of insulin and the lowering of blood glucose levels in diabetic patients. However, the molecular mechanism by which chromium increases insulin sensitivity is not known. Using U937 monocytes as a cell culture model, this study demonstrates that chromium inhibits the secretion of TNF-alpha, a cytokine known to inhibit the sensitivity and action of insulin. U937 cells were cultured with high levels of glucose (mimicking diabetes) in the presence or absence of chromium chloride in the medium at 37 degrees C for 24 h. This study demonstrates that chromium supplementation prevents the increase in TNF-alpha levels and oxidative stress caused by the high levels of glucose in cultured U937 monocytic cells. Similarly, chromium supplementation prevented elevated TNF-alpha secretion and lipid peroxidation levels in H(2)O(2)-treated U937 cells. This study demonstrates for the first time that chromium supplementation inhibits TNF-alpha secretion in U937 monocytes cultured in high-glucose medium, which appears to be mediated by its antioxidative effect. This provides evidence for a novel molecular mechanism by which chromium supplementation may increase insulin sensitivity and glycemic control in diabetic patients.

Antioxidants↗
PubMed1999

Toxicity of chromium to activated sludge.

The work deals with the toxicity of hexavalent and trivalent chromium to activated sludge. Cr(VI) was added as K2Cr2O7, and Cr(III) as Cr2(SO4)3. Toxicity is expressed as the inhibition of respiratory activity of microorganisms present in activated sludge. Respiration was measured by two methods, by means of an oximeter with an oxygen electrode and by means of a manometric apparatus permitting continuous observation of biological oxygen demand (BOD). The equation of the normal distribution function was used to construct inhibition curves and to calculate effective concentration (EC50). The influence of exposure time was observed as was the influence of concentration of activated sludge on the value of EC50. The 1-h EC50 for Cr(VI) by the ISO method was determined to be in the range of 40-90 mg/liter. A greater scatter of measured values, 46-201mg/liter, was found for the first hour of exposure by the manometric method. In the case of Cr(III) only combined inhibition by chromium ions and pH was determined. The 0.5-h EC50 was 49 mg/liter.

Bacteria↗