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Metabolic fate of chromium compounds. I. Comparative behavior of chromium in rat administered with Na251CrO4 and 51CrCl3.

Comparative metabolic fate of labelled chromium chloride and sodium chromate and interaction of these compounds in the rat liver and blood were investigated after their oral and intravenous administration. Gastrointestinal absorption of both compounds was below 1% of the oral dose, but trivalent chromium showed higher radioactivity than the hexavalent form in rats (biological half-life: CrCl3 91.79 days, Na2CrO4 22.24 days). The higher residual activity of the trivalent chromium was also observed after intravenous administration. Both forms of chromium were excreted more in the urine via the kidney than in the intestinal tract after intravenous administration. When 51CrCl3 and Na251CrO4 were injected into rats, in the time-distribution patterns of 51Cr in the organs, a significant difference was shown between oxidation states of the two compounds, especially in subcellular fractions of the liver and blood constituents. This significant difference mainly observed in the rat blood came from the fact that trivalent chromium possessed a high binding activity for transferrin in plasma, while hexavalent chromium was permeable into red cells and bound with hemoglobin.

Animals↗

Uptake of chromium(III) and chromium(VI) compounds in the yeast cell structure.

The study presented in this article investigated the influence of different Cr(III) and Cr(VI) compounds in the cultivation medium on the uptake and localization of chromium in the cell structure of the yeast Candida intermedia. The morphology of the yeast cell surface was observed by the scanning electron microscopy. Results demonstrated that the growth inhibitory concentration of Cr(III) in the cultivation medium induced changes in the yeast cell shape and affected the budding pattern, while inhibitory concentration of Cr(VI) did not cause any visible effects on morphological properties of the yeast cells. The amount of total accumulated chromium in yeast cells and the distribution of chromium between the yeast cell walls and spheroplasts were determined by atomic absorption spectroscopy. No significant differences were found neither in total chromium accumulation nor in the distribution of chromium in yeast cell walls and spheroplasts between the two of Cr(VI) compounds. Conversely, substantial differences between Cr(III) compounds were demonstrated in the total uptake as well as the localization of chromium in yeast cells.

Candida↗

Mechanisms of chromium action: low-molecular-weight chromium-binding substance.

Chromium has long been known to be essential for proper lipid and carbohydrate metabolism in mammals, with chromium deficiency leading to symptoms associated with adult-onset diabetes and cardiovascular disease. Elucidating the structure, function, and mode of action of the biologically active form of chromium has proved enigmatic. However, a naturally-occurring oligopeptide, low-molecular-weight chromium-binding substance (LMWCr), has been found in our laboratory to activate insulin receptor kinase activity up to 7-fold with a dissociation constant of 250 picomolar in the presence of 100 nanomolar insulin, and it has been partially characterized in terms of structural and spectroscopic properties. LMWCr may function in a manner similar to that of the calcium-binding signal protein calmodulin. In other words, LMWCr is maintained in its active apo-oligopeptide form; in response to a chromium flux, LMWCr binds 4 chromic ions. The holoprotein is then capable of binding to insulin receptor (and perhaps other enzymes) activating the enzyme. Establishing a link between the nutrient chromium, LMWCr's activation of insulin receptor kinase activity, and adult-onset diabetes and related conditions could result in a new treatment for these conditions.

Animals↗

Alterations of chromium metabolism and effect of chromium supplementation in Turner's syndrome patients.

This study was conducted to investigate chromium metabolism and the effect of chromium supplementation in patients with Turner's syndrome, a condition noted for its high incidence of diabetes. Oral glucose tolerance tests were performed in 14 patients 8 to 19 yr of age. Eight of the 14 subjects were given 30 g of brewer's yeast containing 50 micrograms of chromium every day for 8 wk and glucose tolerance tests repeated. Urine samples were collected before and after each glucose load. Serum lipids were also investigated. Before supplementation, urinary chromium/creatinine ratio was high, and the urinary chromium response to oral glucose tolerance test was absent. Cholesterol and/or triglyceride levels were high in three of the patients. After supplementation, a decrease in urinary Cr/Cre ratio, and an improvement in glucose area index total were noted. A decrease in cholesterol and/or triglyceride levels occurred in the three patients with high initial levels as well as an increase in high-density lipoprotein cholesterol. These findings indicate a state of chromium deficiency and support the hypothesis that chromium deficiency may have a role in the pathogenesis of the abnormal glucose tolerance tests encountered in Turner patients.

Adolescent↗

Direct determination of chromium(III) and chromium(VI) with ion chromatography using direct current plasma emission as element-selective detector.

A method is described that utilizes direct current plasma atomic emission spectrometry as an element-selective method of detection for ion chromatographic determination of chromium(III) and chromium(VI) species. The eluting chromium-containing species are detected on the basis of the atomic emission of chromium without any species conversion. Both anion and cation separator columns give similar results when used with varying sample matrices. By employing an on-column preconcentration procedure, the detectable concentrations of the chromium species are reduced to less than 1.0 ppb. This method is applied to the determination of chromium species in human serum, natural water, and industrial process stream samples.

Chromatography↗

Effects of chromium picolinate supplementation on body composition, strength, and urinary chromium loss in football players.

The effects of 9 weeks of daily chromium supplementation (200 microgram Cr as picolinate) were investigated in a double-blind design in football players during spring training. Testing was done pre-, mid-, and postsupplementation on the following criterion measures: urinary chromium excretion, girth and skinfold measures, percent body fat and lean body mass, and isometric and dynamic strength. With the exception of 2 variables (of 65 variables analyzed), no significant group by trials interactions were found (based on a repeated measures ANOVA). The two exceptions were unrelated and inconsequential. For 27 of the 38 subjects, average urinary chromium loss at pre was 0.36 microgram/24 hr, whereas it was undetectable (<0.1 microgram/24 hr) for 10 subjects and excessive in 1 subject (2.4 micrograms/24 hr). Subjects receiving chromium supplements demonstrated urinary chromium losses five times greater than those in the placebo group at mid and post. Chromium picolinate supplementation was ineffective in bringing about changes in body composition or strength during a program of intensive weight-lifting training.

Adult↗

[Medicinal plants--concentrators of chromium. The role of chromium in alkaloid metabolism].

Mass screening of medicinal plants of the flora of Russia (196 species) was performed for chromium content. A total of 124 species-chromium concentrators were found, in which the chromium content markedly exceeded the mean values, this excess being 4- to 6-fold in 54 species, 7- to 3-fold in 62 species, and 37- to 114-fold in seven species. The greatest capacity of chromium accumulation was shown for the sand immortelle, foxglove, Alexandrian laurel, Greek valerian, marsh cudweed, adenostilis, and lobelia. These species are considered as potential sources of chromium for correction of its deficiency in humans. Some mechanisms underlying the effect of chromium on metabolism of alkaloids derivative of quinolizidine, tropane, isoquinoline, and indole, were deciphered.

Alkaloids↗

EPR studies of chromium(V) intermediates generated via reduction of chromium(VI) by DOPA and related catecholamines: potential role for oxidized amino acids in chromium-induced cancers.

The reductions of K2Cr2O7 by catecholamines, DOPA, DOPA-beta,beta-d2, N-acetyl-DOPA, alpha-methyl-DOPA, dopamine, adrenaline, noradrenaline, catechol, 1,2-dihydroxybenzoic acid (DHBA), and 4-tert-butylcatechol (TBC), produce a number of Cr(V) electron paramagnetic resonance (EPR) signals. These species are of interest in relation to the potential role of oxidized proteins and amino acids in Cr-induced cancers. With excess organic ligand, all of the substrates yield Cr species with signals at g(iso) approximately 1.972 (Aiso(53Cr) > 23.9 x 10(-4) cm(-1)). These are similar to signals reported previously but have been reassigned as octahedral Cr(V) species with mixed catechol-derived ligands, [CrV(semiquinone)2(catecholate)]+. Experiments with excess K2Cr2O7 show complex behavior with the catecholamines and TBC. Several weak Cr(V) signals are detected after mixing, and the spectra evolve over time to yield relatively stable substrate-dependent signals at g(iso) approximately 1.980. These signals have been attributed to [Cr(O)L2](L = diolato) species, in which the Cr is coordinated to two cyclized catecholamine ligands and an oxo ligand. Isotopic labeling studies with DOPA (ring or side chain deuteration or enrichment with 15N), and simulation of the signals, show that the superhyperfine couplings originate from the side chain protons, confirming that the catecholamine ligands are cyclized. At pH 3.5, a major short-lived EPR signal is observed for many of the substrates at g(iso) approximately 1.969, but the species responsible for this signal was not identified. Several other minor Cr signals are detected, which are attributed (by comparison with isoelectronic V(IV) species) to Cr(V) complexes coordinated by a single catecholamine ligand (and auxiliary ligands e.g. H2O), or to [Cr(O)L2]- (L = diolato) species with a sixth ligand (e.g. H2O). Addition of catalase or deoxygenation of the solutions did not affect the main EPR signals. When the substrates were in excess (pH > 4.5), primary and secondary (cyclized) semiquinones were also detected. Semiquinone stabilization by Zn(II) complexation yielded stronger EPR signals (g(iso) approximately 2.004).

Amino Acids↗

Development of analytical procedures for determination of total chromium by quadrupole ICP-MS and high-resolution ICP-MS, and hexavalent chromium by HPLC-ICP-MS, in different materials used in the automotive industry.

A European directive was recently adopted limiting the use of hazardous substances such as Pb, Hg, Cd, and Cr(VI) in vehicle manufacturing. From July 2003 a maximum of 2 g Cr(VI) will be authorised per vehicle in corrosion-preventing coatings of key components. As no standardised procedures are available to check if produced vehicles are in agreement with this directive, the objective of this work was to develop analytical procedures for total chromium and Cr(VI) determination in these materials. The first step of this study was to optimise digestion procedures for total chromium determination in plastic and metallic materials by inductively coupled plasma mass spectrometry (ICP-MS). High resolution (HR) ICP-MS was used to examine the influence of polyatomic interferences on the detection of the (52)Cr(+) and (53)Cr(+) isotopes. If there was strong interference with m/ z 52 for plastic materials, it was possible to use quadrupole ICP-MS for m/ z 53 if digestions were performed with HNO(3)+H(2)O(2). This mixture was also necessary for digestion of chromium from metallic materials. Extraction procedures in alkaline medium (NH(4)(+)/NH(3) buffer solution at pH 8.9) assisted by sonication were developed for determining Cr(VI) in four different corrosion-preventing coatings by HPLC-ICP-MS. After optimisation and validation with the only solid reference material certified for its Cr(VI) content (BCR 545; welding dusts), the efficiency of this extraction procedure for screw coatings was compared with that described in the EN ISO 3613 standard generally used in routine laboratories. For coatings comprising zinc and aluminium passivated in depth with chromium oxides the extraction procedure developed herein enabled determination of higher Cr(VI) concentrations. This was also observed for the screw covered with a chromium passivant layer on zinc-nickel. For coating comprising a chromium passivant layer on alkaline zinc the standardized extraction procedure was more efficient. In the case of painted metallic plate, because of a reactive matrix towards Cr(VI), its extraction without degradation was difficult to perform.

Journal Article↗

Chromium bond detection in isolated erythrocytes: a new principle of biological monitoring of exposure to hexavalent chromium.

Internal stress to chromium is only relevant in occupational medicine if it is due to the handling of hexavalent chromium. Cr(VI) ions, after uptake by inhalation or percutaneously are carried in the blood plasma and penetrate--depending on the concentration--into the erythrocytes. Due to the intracellular reduction to Cr(III) and the concurrent intracellular protein binding, the erythrocytes represent an easily accessible target organ for quantitative chromium determination after occupational exposure to Cr(VI) compounds. The results of an earlier experimental study indicate that human plasma too is capable of spontaneous reduction of Cr(VI) ions of up to 2 ppm to Cr(III). This plasma reduction capacity (PRC) can be increased and accelerated considerably by adding ascorbic acid (AA). These findings were supported in this investigation by proving a decreased binding of Cr(VI) inside the erythrocytes under the effect of AA. This leads to the assumption that only those Cr(VI) concentrations can penetrate the membrane of the erythrocytes and enter the cell which either come into contact with the membrane during the reduction process or exceed this limit concentration of 2 ppm. Only in these two instances can corresponding chromium findings be analyzed in isolated and washed erythrocytes. These results are compared with those obtained by conventional methods, such as Cr determination in the blood and/or urine. Our findings indicate that a single determination of chromium concentration in the erythrocytes will permit the monitoring of critical cases of Cr(VI) exposure. This is a new type of biological monitoring in the sense of a condensed longitudinal study, in order to find out whether threshold concentrations have been respected over a given period.

Air Pollutants, Occupational↗

Chromium in plants. Comparison between the concentration of chromium in Brazilian nonhypo and hypoglycemic plants.

Chromium is an essential trace element and is associated with some biological pathways, especially with glucose tolerance. For these reasons, we decided to determine the concentration of chromium in two sets of Brazilian medicinal plants. The first group consisted of plants that are considered as antidiabetic, whereas the second included plants that do not have this therapeutic property. The concentration of chromium was determined by flameless atomic absorption. All the plants analyzed contain chromium in the normal range for this element, but the hypoglycemic plants contain more chromium than the others (1-4 micrograms/g compared to 0.5-1.5 micrograms/g).

Brazil↗

Preconcentration of chromium (III) and speciation of chromium by electrothermal atomic absorption spectrometry using cellulose adsorbent.

A simple and sensitive method has been developed for species selective determination of chromium(III) and chromium(VI) in water by electrothermal atomic absorption spectrometry. The procedure is based on selective absorption of Cr(III) on a cellulose micro column (pH 11, 0.5 mol L(-1) NaCl). Total chromium was subsequently determined after appropriate reduction of Cr(VI) to Cr(III). Recoveries of more than 97% were found. A concentration factor of 100 was achieved. The relative standard deviations (n=10) at the 40 ng L(-1) level for chromium(III) and chromium(VI) were 2.3% and 1.8% and corresponding limits of detection (based on 36) were 1.8 ng L(-1) and 5.1 ng L(-1), respectively. No interference effects have been observed from other investigated species and the method has been successfully applied to natural water samples.

Cellulose↗

Mechanisms of formation and decomposition of hypervalent chromium metabolites in the glutathione-chromium (VI) reaction.

A long-lived chromium(IV) intermediate is generated during the reaction between Cr(VI) and glutathione in glycine below pH 3. The intermediate reacts with the tripeptide to produce Cr(III) and oxidized glutathione. A dynamic magnetic susceptibility measurement based on a nuclear magnetic resonance method yielded a 2.8 microB magnetic movement for the chromium(IV) species. The intermediate is formed by parallel third-order and second-order processes. The third-order process (k = 5.9 x 10(2) M-2 s-1) involves first-order participation by each of the oxidant, reductant, and hydrogen ions. A hydrogen ion independent pathway leads to a sluggish second-order process (k = 0.11 M-1 s-1) that is first order with respect to reduced glutathione [GSH] and [Cr(VI)]. Chromium(IV) species is reduced to Cr(III) by a second-order process (k = 0.13 M-1 s-1) that is first order in each of [Cr(IV)] and [GSH] and does not depend on [H+]. At pH 3.4, a chromium(V) species was detected as a minor intermediate as well. In the pH range 6.5-7.5, three dominant chromium(V) intermediates were detected. The existence of Cr(IV) in low pH offers an opportunity to examine the mechanism of DNA damage by this rare oxidation state.

Chromium↗

Whole blood chromium level and chromium excretion in the rat after zinc chromate inhalation.

Studies on absorption and excretion of chromium in the rat exposed to known atmospheric concentrations of zinc chromate in an inhalation chamber and the influence of diurnal variations in physical activity have been carried out. Chromium analyses were performed on samples of blood, urine and faeces using a method for determining chromium in small samples of biological material based on flameless atomic absorption spectrometry. Zinc chromate is absorbed quickly during exposure and excreted mainly via urine. An accumulation of chromium in blood was observed, followed by a slow elimination. It is suggested that chromium from zinc chromate enters the blood in the hexavalent state.

Animals↗

Stability and absorption of chromium and absorption of chromium histidinate complexes by humans.

Increased intake of chromium (Cr) often leads to improvements in glucose, insulin, lipids, and related variables in studies involving humans and experimental and farm animals. However, the results are often variable, depending not only on the selection of subjects but also dietary conditions and the form of supplemental Cr used. Our objective was to find a Cr supplement suitable for humans that was absorbed better than any of those available. Chromium absorption by six adult subjects, three males and three females, was determined based on the amount of Cr excreted in the urine in the initial 2 d following intake of 200 microg of Cr of the various forms of chromium tested. The absorption of the newly synthesized complexes was greatest for those containing histidine. Urinary Cr losses for six control subjects consuming 200 microg of Cr as Cr histidinate increased from basal levels of 256+/-48 to 3670+/-338 ng/d compared with 2082+/-201 ng for Cr picolinate, the currently most popular nutrient supplement, in the 48 h following Cr consumption. Chromium histidinate complexes were stable and absorption was similar to the initial values after more than 2 yr. Mixing of some of the complexes with starch, which was postulated to improve Cr absorption, was shown to essentially block Cr absorption within 1 mo. These data demonstrate that urinary Cr losses need to be determined because stability and absorption of the Cr complexes varies widely and could be responsible for the variability in some of the Cr supplementation studies. Chromium histidinate complexes are absorbed better than any of the Cr complexes currently available and need to be evaluated as Cr nutritional supplements.

Adult↗

Effects of taurine on oxidative stress parameters and chromium levels altered by acute hexavalent chromium exposure in mice kidney tissue.

The kidney has been regarded as a critical organ of toxicity induced by acute exposure to hexavalent chromium [Cr(VI)] compounds. Reactive intermediates and free radicals generated during reduction process might be responsible for Cr(VI) toxicity. In this study, the effects of pretreatment or posttreatment of taurine on Cr(VI)-induced oxidative stress and chromium accumulation in kidney tissue of Swiss albino mice were investigated. Single intraperitoneal (ip) potassium dichromate treatment (20 mgCr/kg), as Cr(VI) compound, significantly elevated the level of lipid peroxidation as compared with the control group (p<0.05). This was accompanied by significant decreases in nonprotein sulfhydryls (NPSH) level, superoxide dismutase (SOD), and catalase (CAT) enzyme activities as well as a significant chromium accumulation (p<0.05). Taurine administration (1 g/kg, ip) before or after Cr(VI) exposure resulted in reduction of lipid peroxidation levels and improvement in SOD enzyme activity (p<0.05). On the other hand, administration of the antioxidant before Cr(VI) exposure restored the NPSH level and CAT enzyme activity and also reduced tissue chromium levels (p<0.05), whereas posttreatment had only slight effects on these parameters. In view of the results, taurine seems to exert some beneficial effects against Cr(VI)-induced oxidative stress and chromium accumulation in mice kidney tissue.

Animals↗