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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↗

Chromium(III) induced abnormalities in human lymphocyte cell proliferation: evidence for apoptosis.

The occupational hazards and respiratory problems of workers associated with the chromium related industries like mining, electroplating and tanning have received much focus. Although the cytotoxic and mutagenic effects of common chromium(VI) compounds are now established, to the best of our knowledge, this is the first report of apoptosis (programmed cell death) caused by a set of Cr(III) complexes in human lymphocyte cells. The effects of five Cr(III) complexes with differing ligand environment and structure as well as K2Cr2O7 on Phytohaemagglutinin (PHA) induced lymphocyte cell proliferation have been investigated. Two of the Cr(III) complexes and K2Cr2O7 are found to cause apoptosis of lymphocytes but not the others. A case for the importance of species specific effects rather than non specific metal oxidation state dependent processes has now been made.

Apoptosis↗

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↗

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↗

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↗

Light intensity influences chromium bioaccumulation and toxicity in Scenedesmus acutus (Chlorophyceae).

The influence of light intensity on chromium uptake was studied in two strains of the freshwater unicellular alga Scenedesmus acutus (Chlorophyceae) having different sensitivity to Cr poisoning and light intensity. The two strains were subjected to different Cr treatments at 3000 and 80 lux. Cr toxicity was assessed by algal growth rate, recovery test, methylene blue staining, and determination of photosynthetic activity. After 2 and 4 days of treatment, bioaccumulated chromium, cell dry mass, and protein and carbohydrate contents were also assessed. When the algae were treated at 3000 lux, different bioaccumulation patterns were obtained when Cr content was related to dry mass, cell number, or protein content. A direct relationship between Cr content and cell mortality was observed only when the amount of Cr was related to protein content. In both strains Cr uptake was slower in subdued light, suggesting that it is linked to energy-dependent processes. The difference between the strains in sensitivity to Cr poisoning was also evident in subdued light.

Cell Death↗

In vitro reduction kinetics of hexavalent chromium in human blood.

This study examines time- and concentration-dependent changes in distribution of hexavalent chromium [Cr(VI)] and total chromium [Cr-(TOT)] in reconstituted human blood following addition of potassium dichromate. Fresh human blood stabilized with EDTA was obtained from human volunteers soon after meal ingestion and at 2.5 h after a light meal (herein defined as "2.5-h fasted" conditions). Cr(VI) spiked into plasma under 2.5-h fasting conditions at 3.0-12.5 micrograms/L was stable for several hours, indicating a lack of appreciable reductive capacity in isolated plasma. Spiked plasma following a recent meal exhibited immediate but variable reduction of Cr(VI) up to 300 micrograms/L. When the spiked plasma was recombined with the red blood cell (RBC) fraction, rapid reduction occurred in both the plasma and the RBC fractions based on measurement of Cr(VI) and Cr(TOT). The data indicate that plasma reduction capacity is enhanced by a recent meal, but may be overwhelmed at Cr(VI) concentrations between 2000 and 10,000 micrograms/L. These data also suggest that the RBC fraction apparently has the capacity to reduce Cr(VI) at concentrations in blood up to 15,000 micrograms/L, and that the rate of Cr(VI) uptake into RBCs may not exceed the rate of intracellular reduction at these concentrations.

Chromates↗

Impurity nuclear spin-lattice relaxation suppression and charge exchange of chromium ions in a gamma-irradiated ruby crystal.

The possibility of directly separating and measuring the impurity and lattice contributions to nuclear spin-lattice relaxation under the condition of a steady-state magnetic saturation is demonstrated in the particular case of 27Al nuclei in a gamma-irradiated ruby crystal. Contributions from trivalent and charge-exchanged chromium ions to impurity nuclear relaxation were separated. The number of charge-exchanged chromium ions was found. The spin relaxation time of Cr4+ centers was estimated.

Chromium↗

Heavy metals mercury, cadmium, and chromium inhibit the activity of the mammalian liver and kidney sulfate transporter sat-1.

Heavy metal intoxication leads to defects in cellular uptake mechanisms in the mammalian liver and kidney. We have studied the effects of several heavy metals, including mercury, lead, cadmium, and chromium (at concentrations of 1 to 1000 microM), on the activity of the mammalian sulfate transporter sat-1(2) in Xenopus oocytes. sat-1 encodes a sulfate/bicarbonate anion exchanger expressed in the rat liver and kidney. Mercury (10 microM) strongly inhibited sat-1 transport by reducing Vmax by eightfold but not its Km for inorganic sulfate (Si). Lead (up to 1 mM) was unable to significantly inhibit sat-1 transporter activity. Cadmium (500 microM) showed weak inhibition of sat-1 transport by decreasing only sat-1 Vmax. Chromium (100 microM) strongly inhibited sat-1 transport by reducing Km for Si by sevenfold, most probably by binding to the Si site, due to the strong structural similarity between the CrO2-4 and SO2-4 substrates. This study presents the first characterization of heavy metal inhibition of the hepatic and renal sulfate/bicarbonate transporter sat-1, through various mechanisms, which may lead to sulfaturia following heavy metal intoxication.

Algorithms↗

Preconception urethane or chromium(III) treatment of male mice: multiple neoplastic and non-neoplastic changes in offspring.

Increase in neoplasia in offspring after preconception exposure of parents presents puzzling features such as high frequency of effects and lack of Mendelian inheritance. The present study examined the hypothesis that preconception carcinogenesis involves an increase in the rate of occurrence of neoplasms with a spontaneous incidence. Male NIH Swiss mice (12 per group) were exposed 2 weeks before mating (once, ip) to urethane (1.5 g/kg) or chromium(III) chloride (1 mmol/kg). Offspring (48-78/sex/group) were examined for all grossly apparent changes when moribund or at natural death, followed by histopathological diagnosis and statistical analysis. Significant exposure-related changes occurred in multiple organs. Ten to 20 percent of offspring showed changes related to paternal exposure, including at least one sired by most treated males. Pheochromocytomas occurred in both male and female offspring after both treatments, with none in controls. These neoplasms are rare in mice and suggest endocrine dysfunction as a component of preconception carcinogenesis. This was supported by increases in thyroid follicular cell and Harderian gland tumors, ovarian cysts, and uterine abnormalities. Lung tumors were increased in female offspring only. Effects seen in offspring only after paternal urethane exposure were an increase in preneoplasia/neoplasia in the glandular stomach (males) and in females, increased lymphoma but decreased incidence of histiocytic sarcoma. Increases in incidence of male reproductive gland tumors and of renal non-neoplastic lesions occurred only after chromium exposure. Thus, preconception exposure of fathers to toxicants had a significant impact on both neoplastic and non-neoplastic changes in almost all tissues in which these lesions often occur naturally during the aging process.

Adenoma↗

Sensitive quantitation of chromium-DNA adducts by inductively coupled plasma mass spectrometry with a direct injection high-efficiency nebulizer.

A novel method is described for the sensitive detection of chromium-DNA adducts. Chromium-DNA adducts were determined in 1 microgram of DNA from normal human lung fibroblasts exposed to sodium chromate using microscale flow injection analysis with a direct injection high-efficiency nebulizer and inductively coupled plasma mass spectrometry detection. The frequency of Cr-DNA adducts increased in a dose-dependent sigmoidal manner, indicating saturation and toxicity. The low detection limits (on the order of parts per trillion) allows the detection of as few as two Cr adducts per 10,000 bases, which, coupled with the small DNA sample requirement, makes this technique suitable for measuring metal-DNA adducts as biomarkers of exposure to toxic and carcinogenic metals such as Cr, in cultured cells, animals, and humans.

Chromium↗

Effects of carbohydrate loading and underwater exercise on circulating cortisol, insulin and urinary losses of chromium and zinc.

The effects of carbohydrate loading on relative stress responses of eight male subjects performing intermittent leg exercise at 80% maximum oxygen consumption during headout immersion in 25 degrees C water were tested. Carbohydrate loading increased the number of work cycles completed, with less physical stress compared with that completed following the control diet period. Pre-exercise serum cortisol values were similar on both diets prior to exercise but following exercise control values were greater (1152, 94 vs 858, 77 nmol l-1; mean, SEM). Chromium losses, which have been shown to correlate with stress, were lower during the carbohydrate loading period, 8.6, 1.3 vs 12.4, 2.0 ng h-1, and were correlated with post-exercise serum cortisol. Urinary zinc losses were also lower during carbohydrate loading, while urinary losses of potassium, magnesium and calcium remained constant. Insulin values decreased similarly following exercise in both groups and were not altered by carbohydrate loading. These data demonstrate that carbohydrate loading increases immersion exercise output with less stress as determined by serum cortisol and urinary chromium losses.

Adult↗

Trace element burdening of human tissues due to the corrosion of hip-joint prostheses made of cobalt-chromium alloys.

Using instrumental neutron activation analysis, the concentrations of 18 elements were studied in human articular capsule and fascia lata before and after application of total endoprostheses of the hip joint made of cobalt-chromium alloys. Tissues from the vicinity of the implant showed extreme burdening by corrosion products (Co, Cr, Ni), as well as by Zr, Hf, and Ba from the bone cements. Tissues more distant from the implants exhibited lower, but still significant burdening. Moreover, some essential trace elements not contained in the implant materials were changed in the tissues after implantation. In order to clarify the dissolution of alloy constituents in biological media, the passivation of cobalt-chromium alloy was investigated by tracer techniques using Ringer's solution as a simple model of the body fluids. The passivation process lasted for more than 1 month and was accompanied by a selective dissolution of the alloys constituents in the order Ni greater than Co approximately Fe greater than Mo greater than Cr. A comparison of the tissue analyses with the corrosion experiments demonstrates that the distribution patterns of the corrosion products in the tissues are influenced by both the corrosion process and the biochemical properties of the corrosion products.

Adult↗

Urinary N-acetyl-beta-D-glucosaminidase and beta-aminoisobutyric acid in workers occupationally exposed to metals such as chromium, nickel, and iron.

To examine the relationships between the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and beta-aminoisobutyric acid (AIBA) as a metabolite of thymine, and exposure to chromium, nickel, and iron, we determined these parameters in 58 workers engaged in the cutting and grinding of stainless steel or iron-steel plates. A significant increase in urinary NAG activity or urinary AIBA excretion was found in some of these workers. However, we could not find a significant positive correlation between the urinary excretion of NAG or AIBA and the urinary concentration of chromium, nickel, or iron as an indicator of internal dose.

Acetylglucosaminidase↗

Phagocytosis of chromium during patellar osteoarthritic remodelling associated with a knee prosthesis.

The report is of an anatomico-pathological and electron probe microanalyzer study of a patella with osteoarthritic remodelling, that had been in contact with a cast cobalt-chromium-molybdenum prosthesis for two years and seven months. Abrasion of the metal resulted in preferential phagocytosis of chromium, principally in the wall of an osteoarthritis cyst. This observation indicates that a substance administered by intra-articular pathway for the treatment of osteoarthritis can become phagocytosed, and quite deeply, in the remodelled bone.

Aged↗

Toxicity of chromium and tin to Anabaena doliolum. Interaction with sulphur-containing amino acids and thiols.

Toxicity of chromium and tin on growth, heterocyst differentiation, nitrogenase activity and 14CO2 uptake of Anabaena doliolum and its amelioration by sulphur-containing amino acids and thiols has been studied. The final growth yield was found to be approximately 51% and 58% of control at sublethal concentration of chromium and tin respectively. Among various amino acids tested, cysteine (0.05 mM) significantly restored growth, heterocyst differentiation, nitrogenase and 14CO2 uptake of test alga. Dithiothreitol (1 mM) restored all the parameters and processes better than monothiol, mercaptoethanol. It is obvious from present investigation that sulphur-containing amino acids and thiols, viz. cysteine, methionine, cystine, mercaptoethanol and dithiothreitol, may appreciably alleviate the toxicity of heavy metals in N2-fixing cyanobacteria if present in an aquatic ecosystem.

Amino Acids, Sulfur↗

Daily dietary chromium intake in Belgium, using duplicate portion sampling.

Daily dietary chromium intake in Belgium has been evaluated by sampling duplicate portions of food, heating them at an acidic pH in a microwave oven and then quantifying the chromium by atomic absorption spectrometry. The mean intake value (53 +/- 31 micrograms/day) is similar to levels found for most other countries and is situated at the lower end of the recommended range for a safe and adequate daily dietary intake.

Belgium↗

[Condition of supply of Austrians with the trace element chromium].

A duplicate diet study to determine the daily chromium intake of Austrians was made. Ten probands (five women and five men) collected the same as they ate seven days running. The mean chromium intake of these probands was 34.5 micrograms per day with a range of 28.5 micrograms up to 44.7 micrograms, the mean intake of the women was 31.4 micrograms and of the men was 37.6 micrograms. This value indicates a suboptimal supply status and shows a good agreement with an Austrian estimation of the daily dietary intake from 200 single foods.

Adolescent↗