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[IR-spectroscopic study of the interaction of chromium salts with native DNA].

Infrared spectra of some unoriented films of DNA contained CrCl3, K2Cr2O7 and Cr2(SO4)3 have been obtained at relative humidities (r.h.) 0 to 93%. Chromium cations were shown to interact with phosphoric groups of DNA molecules. Cr2(SO4)3 or K2Cr2O7 content exceeds 0.1 Cr/P, the sugar-phosphate backbone of the double helix becomes irregular and nucleic bases unstacked, i.e. denaturation of DNA occurs. A very small amount of the salt, less than 0.01 Cr/P contained in DNA films prevents the conformational transition of the double helix from the B to A form induced by r.h. decreasing. The efficiency of the chromium salts in preventing the transition falls in the row: Cr2(SO4)3 > K2Cr2O7-CrCl3.

Animals↗

Induction of mutagenic DNA damage by chromium (VI) and glutathione.

Certain chromium (Cr) compounds are known to be carcinogenic in humans and mutagenic in cell culture. However, the mechanism of Cr mutagenesis is not well understood. It appears that intracellular reduction of Cr by agents such as glutathione plays a role in the induction of DNA damage. We have used a simian virus 40-based shuttle vector to investigate the relationship between chromium-induced DNA damage and Cr mutagenicity. The treatment of the plasmid pZ189 with Cr(VI) plus glutathione (GSH) induced DNA strand breaks and reduced the plasmid biological activity, whereas Cr(III) treatment with or without GSH did not give rise to such DNA damage. When Cr(VI)/GSH- or Cr(III)/GSH-treated pZ189 was replicated in mammalian cells, a dose-dependent increase in mutant frequency was observed with Cr(VI)/GSH-treated pZ189, but not with Cr(III)/GSH-treated plasmid. About 43% of the mutants from Cr(VI)/GSH-treated pZ189 were deletion mutants. The remainder were base substitution mutants, mostly GC-->AT transitions and GC-->TA transversions. This pattern of mutagenesis is similar to that observed with other agents that cause oxidative DNA damage such as ionizing radiation and H2O2. These results support the hypothesis that Cr mutagenesis can be induced by the generation of reactive oxygen intermediates during the reduction of Cr(VI) by glutathione.

Animals↗

Chromium status of tannery workers in relation to metabolic disorders.

Chromium (Cr), being an excellent tanning agent, is widely used in the leather industry. In the process of leather production, tannery workers are exposed to either inorganic Cr(III) compounds or Cr bound to proteins (leather dust). The total Cr content in tannery air (1-54 microg m(-3)) is rather high in comparison to ambient air (4-6 ng m(-3)) but the amount of Cr in inhalable particles (<10 microm) is two to three orders of magnitude less (20-60 ng m(-3)). The total daily intake of Cr was estimated by the analysis of diet (24.3 +/- 4.0 microg Cr day(-1)), drinking water (0.3 +/- 0.1 microg Cr dm(-3)) and ambient air. The contribution of the latter was dominant for tannery workers and almost negligible (8%) for the unexposed population. Chromium is an essential nutrient required for sugar and fat metabolism. The normal dietary intake of Cr for the occupationally unexposed population is found to be suboptimal (<30 microg Cr day(-1)) whereas tannery workers receive on average 150-325 microg of supplemental Cr day(-1). Assessment of the Cr status of both populations was made on the basis of the Cr contents of their scalp hair, pre-shift urine and thermally induced sweat. The median Cr contents in these tissues and fluids were significantly higher (P<0.01) in tannery workers (hair: 4 microg Cr g (-1), urine: Cr/creatinine 1.7 microg Cr g(-1), sweat: 25 microg Cr dm(-3)) in comparison with the control group (hair: 0.16 microg Cr g(-1), urine: Cr/creatinine 0.13 microg Cr g (-1), sweat: 0.7 microg Cr dm(-3)). Tannery workers absorbed up to 13 times more Cr in comparison to controls, the amount varying considerably depending on the workplace and duration of exposure. The main route of Cr absorption appears to be through the gastrointestinal tract, where medium to large particles play a dominant role. The absorption of Cr from leather dust may be more efficient in comparison to inorganic Cr(III) compounds. Under normal circumstances sweat Cr losses represent at least 20% of urinary Cr excretion. The incidence of glucose intolerance and disturbed lipid metabolism was compared between the unexposed (control) population (n=150) and a population of tannery workers (n=138) from the same residential area. The percentage of glucose-intolerant subjects was significantly (P<0.01) lower in the older subgroup (age>48 years), who were even more obese, but not in the whole tannery population in comparison to controls. In the group of subjects displaying glucose intolerance, those from the control population showed a significantly higher body mass index (BMI) of 32.3 and a considerably larger proportion of females (86%) in comparison to subjects from the tannery population (28.2 and 60%, respectively). There was no significant difference in total serum cholesterol levels between the groups. Results of other lipid variables, such as high-density lipid (HDL) cholesterol, low-density lipid (LDL) cholesterol and triglycerides, are controversial: namely, the HDL/LDL ratio was higher for the controls, who showed in contrast significantly higher serum triglyceride levels in comparison to the older subgroup of tannery workers. The possible effects of other parameters on serum HDL-cholesterol level are outlined but the influence of Cr on lipid metabolism in tannery workers remains unclear.

Adult↗

Chromium speciation by surfactant assisted solid-phase extraction and flame atomic absorption spectrometric detection.

A new procedure has been developed for chromium speciation in aqueous solution by the use of micellar, ion-association, solid-phase extraction techniques (SPE) followed by flame atomic absorption spectrometry. The method was based on the use of C-18 bonded phase silica SPE disks for retention of ion-associated Cr(VI) with cetyl trimethyl ammonium bromide (CTAB), elution of the retained species and subsequent detection by flame atomic absorption spectrometry (FAAS). Cr(III) was oxidized by potassium persulfate to Cr(VI), then the total chromium was retained on the disk and determined by FAAS. The amount of Cr(III) was calculated by the difference between the total and Cr(VI) values. The calculated limit of detections (LOD) (based on 3sigma) are 15 microg L(-1) and 20 microg L(-1) for Cr(VI) and Cr(III) respectively. No considerable interferences have been observed from other investigated anions and cations and the method has been successfully applied to water samples taken from the Karoon River in Khuzestan province.

Chromium↗

Studies and application of catalytic kinetic spectrophotometric determination of trace chromium(VI) sensitized by microemulsion medium.

A new catalytic kinetic spectrophotometric method for the determination of trace amount of chromium (VI) in microemulsion medium has been developed. The method is based on the catalytic effect of chromium (VI) on the oxidation of nuclear fast red in the presence of Tween-80 microemulsion and HAc-NaAc buffer solution (pH = 5.2). The linear ranges are in the range of 0 approximately 0.0480 microg mL(-1) of Cr (VI) at 528 nm and the detection limit is 1.56x10(-9)g mL(-1). The method has been applied in determination of Cr (VI) in water and food samples with satisfactory results. The relative standard deviation is less than 4.6 % and the recovery is 93.5 approximately 104 %.

Acetic Acid↗

Impairment of cell and plasma redox state in subjects professionally exposed to chromium.

BACKGROUND: Chromium (Cr) is widely used in chemical, tannery, building, and metal industries. More recently, it has been demonstrated that Cr induces oxidative stress in mouse brain. Nevertheless very few data exist on in vivo oxidative damage in humans exposed to Cr. METHODS: Changes in antioxidant parameters both in plasma (acid ascorbic redox state and total antioxidant capacity) and in red blood cells (glutathione (GSH) redox state) of 40 subjects (age 37.65 +/- 7.46; M/F 20/20) professionally exposed to Cr who were recruited from metal, chemistry, and building industries were evaluated. We also evaluated the levels of lipoperoxidation (thiobarbituric acid-reactive material, TBA-RM) and thiol levels in plasma to assess the extent of oxidative stress state. To evaluate Cr exposure rate, we measured urinary-chromium (U-Cr) by an electrothermic atomization-atomic absorption spectrometry (ETA-AAS) method. RESULTS: In this study, we found that Cr exposure induced a decrease both in GSH (P < 0.0005) and GSH/oxidized glutathione (GSSG) ratio (P < 0.0001) in red blood cells from workers with respect to control subjects. Furthermore, we also demonstrated a significant decrease of plasma acid ascorbic levels (45.7 +/- 14.9 vs. 53.5 +/- 16.5 micromol/L; P < 0.05) and in total plasma antioxidant capacity (1,126.3 +/- 212.2 vs. 1,266.9 +/- 207.8 micromol/L; P < 0.05) in subjects exposed to Cr. No difference was found with regard to TBA-RM and thiol levels. CONCLUSIONS: This study demonstrated that in humans, an oxidative stress occurs for Cr exposures as low as those considered safe. This oxidative stress appears to be able to affect intracellular and plasmatic antioxidant defense.

Adult↗

Increased chromium and nickel content in lung tissue and bronchial carcinoma.

In 25 random autopsies, chromium (Cr) and nickel (Ni) in lung tissue and regional lymph nodes were analysed by means of flameless atomic absorption spectrometry (AAS). The subjects originate from Bochum in the Ruhr District, which is defined as a particular pollution area with locally high Cr and Ni emissions. The subjects examined from Bochum (BO) and vicinity have Cr and Ni concentrations about 5 and 6 times higher than those in a previous series form Münster (MS) and vicinity (outside the particular pollution area), which is used for comparison purposes. BO and MS data showed an age-dependent increase of chromium and nickel in the lung, and in both data sets as well as in the combined, the Cr and Ni values showed extremely high correlations (r greater than 0.9). The Cr and Ni concentrations (BO) in lung (3.47 +/- 2.53 micrograms Cr/g, 1.09 +/- 1.43 micrograms Ni/g dry weight) and lymph node tissue (6.30 +/- 3.72 micrograms Cr/g, 1.00 +/- 0.58 micrograms Ni/g dry weight) do not show any correlation. The BO data contained four cases of bronchial carcinoma (all male), three of which showed pulmonary Cr and Ni concentrations that lie clearly above the predicted level. One case of bronchial carcinoma had extremely high Cr and Ni values; an occupational exposure as dental laboratory technician is taken into consideration.

Carcinoma, Bronchogenic↗

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↗

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↗

Experimental efficacy of an everolimus eluting cobalt chromium stent.

INTRODUCTION: Rapamycin and its analogs are now being coated on different stent platforms, using different polymer matrices to prevent restenosis by impairing vascular smooth muscle cell proliferation and neointimal formation. METHODS: We evaluated the feasibility and compared the efficacy of biostable polymeric everolimus and sirolimus (CYPHER, Cordis) eluting stents in a porcine coronary model. Cobalt chromium balloon expandable stents (ML VISION, Guidant) were coated with a polymer containing everolimus (190 mug/cm(2)). Twelve pigs underwent placement of 36 oversized sirolimus (n = 12), everolimus (n = 12), and bare metal (cobalt chromium, n = 12) stents in the coronary arteries. RESULTS: At day 28, vessel injury scores were low (<0.25) and similar between each of the three test groups. The mean neointimal thickness was significantly lower in the everolimus- (0.13 +/- 0.07 mm, P = 0.02) and sirolimus-eluting stents (0.13 +/- 0.08 mm, P = 0.04) versus the bare metal stents (0.20 +/- 0.07 mm). The mean percent area stenosis was similar for the everolimus-eluting stents [(20.8 +/- 6.9)%] and the sirolimus-eluting stents [(20.8 +/- 7.6)%], and each was significantly less than that of bare metal stents [(26.1 +/- 7.8)%, P = 0.05]. CONCLUSION: Stent-based delivery of sirolimus and everolimus delivered via durable polymeric matrices are equally effective in the suppression of neointimal formation at day 28 in the porcine coronary model. Further study is necessary to document dose response and long-term comparative effects of these drug-eluting stents.

Animals↗

Protective effect of vitamin B6 in chromium-induced oxidative stress in liver.

The aim of this study was to examine the efficacy of vitamin B6 against chromium (Cr)-induced oxidative stress. Adult male albino Wistar rats (100-120 g) were used in this study. Potassium dichromate, a Cr VI compound, was administered at a dose of 127 mg kg(-1) p.o. Vitamin B6 (pyridoxine hydrochloride) was administered at a dose of 100 mg kg(-1) p.o. either alone or 12 h prior to Cr or simultaneously with Cr. Chromium treatment induced oxidative stress in the liver as measured by increased lipid peroxidation (LPO) and decreased vitamin C, vitamin E, glutathione (GSH), glutathione peroxidase (GPX), catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST) and glutathione reductase (GR). Both pre- and simultaneous treatments countered Cr-induced oxidative stress; pre-treatment was more effective than concurrent administration. The results demonstrate the antioxidant potential of vitamin B6.

Animals↗

Cast vs. wrought cobalt-chromium surgical implant alloys.

The measured tensile and fatigue strengths of wrought and heat-treated cobalt chromium-molybdenum-carbon alloys such as HS21 were found to be more than twice those of as cast alloys of the same composition. The resistance of wrought HS21 to crevice corrosion at metal-Teflon contacts in isotonic salt solution at 37 degrees C was found to be considerably greater than that of cast HS21, wrought HS25, wrought MP35, or 316L stainless steel which are currently used for surgical implants. The increased crevice corrosion resistance and mechanical strength of wrought HS21 as compared to as cast HS21 was attributed to greater chemical and structural homogeneity as well as to finer grain size and distribution of secondary phases. Fabrication of shaped implants from wrought HS21 is possible by techniques currently used for the fabrication of industrial parts from other wrought cobalt-chromium base alloys.

Carbon↗

Component wear of total knee prostheses using Ti-6A1-4V, titanium nitride coated Ti-6A1-4V, and cobalt-chromium-molybdenum femoral components.

A knee simulator was used to study the wear of carbon fiber reinforced UHMWPE (Poly Two) (Poly Two is a registered trademark of Zimmer, USA) tibial and patellar components against Ti-6A1-4V, titanium nitride (TiN)-coated Ti-6A1-4V, and cobalt-chromium-molybdenum femoral components. The prostheses tested were regular sized Miller-Galante total knees mounted on 316L stainless steel fixtures using bone cement. An environmental chamber surrounded the knee and maintained bovine serum lubricant at 37 degrees C. The specimens were tested using consecutive blocks of 464 level walking steps, 8 ascending stairs and 8 descending stairs for a total of 100,000 steps. The wear mechanisms found on the tibial components were scratching, carbon-fiber associated damage, surface deformation, pitting, minor abrasion, and delamination. Three forms of carbon fiber associated damage were identified; fibers pulled from the surface, broken fibers, and UHMWPE removed from the surface fibers. The SEM evaluation revealed a pit forming mechanism. No correlation was found between femoral component material and tibial surface damage. Visual examination of the femoral components revealed no signs of wear or scratching on the cobalt-chromium-molybdenum or TiN-coated Ti-6A1-4V components. There were, however, many light surface scratches on the uncoated Ti-6A1-4V components, which were also observed in a supplementary test of an uncoated Ti-6A1-4V component tested with a conventional polyethylene tibial component.

Alloys↗

Mechanical strength of laser-welded cobalt-chromium alloy.

The purpose of this study was to investigate the effect of the output energy of laser welding and welding methods on the joint strength of cobalt-chromium (Co-Cr) alloy. Two types of cast Co-Cr plates were prepared, and transverse sections were made at the center of the plate. The cut surfaces were butted against one another, and the joints welded with a laser-welding machine at several levels of output energy with the use of two methods. The fracture force required to break specimens was determined by means of tensile testing. For the 0.5-mm-thick specimens, the force required to break the 0.5-mm laser-welded specimens at currents of 270 and 300 A was not statistically different (p > 0.05) from the results for the nonwelded control specimens. The force required to break the 1.0-mm specimens double-welded at a current of 270 A was the highest value among the 1.0-mm laser-welded specimens. The results suggested that laser welding under the appropriate conditions improved the joint strength of cobalt- chromium alloy.

Biocompatible Materials↗

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↗

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↗

Mixed-mode fracture toughness of the cobalt-chromium alloy/polymethylmethacrylate cement interface.

Mechanical debonding of the stem/cement interface has been implicated in the failure process of cemented femoral hip components. The nature of this failure process remains poorly understood due, in part, to limited understanding of how interfacial debonding occurs in response to a wide range of loading conditions. The purpose of this investigation was to determine the fracture toughness of the cobalt-chromium alloy/polymethylmethacrylate interface under mixed-mode loading conditions. The hypothesis was that the critical energy release rate was dependent on the phase angle of the crack tip and that the fracture response would be significantly different for a smooth compared with rough interface surface. A novel in-plane shear test fixture was developed with use of a combination of finite element and experimental fracture-mechanics tests. A wide range (-65-60 degrees) of phase angles was determined with the in-plane shear test and a clamped cantilever-beam test. Sixty experimental tests were performed for cobalt-chromium alloy bars with a plasma-sprayed coating or a precoat of polymethylmethacrylate over a satin-finished surface. For the specimens with the plasma-sprayed coating, critical energy release rates (500-700 J/m2) were not a function of the phase angle of the crack tip. In contrast, critical energy release rates (15-80 J/m2) were found to be strongly affected by the phase angle for the specimens precoated with polymethylmethacrylate. The critical energy release rate for specimens with the plasma-sprayed surface was significantly (p < 0.01) greater than for those precoated with polymethylmethacrylate. The critical energy release rate increased markedly with the phase angle of the crack tip for the specimens precoated with polymethylmethacrylate. The results suggest that the failure response of a stem with a plasma-sprayed surface may be insensitive to the loading angle of the crack tip, whereas a stem precoated with polymethylmethacrylate may be more likely to debond under tensile opening loading.

Alloys↗

Inhibition of NF-kappa B binding to DNA by chromium, cadmium, mercury, zinc, and arsenite in vitro: evidence of a thiol mechanism.

NF-kappa B binding to DNA in the presence of thiol-reactive metals has been explored in vitro. Gel mobility shift assays using total nuclear extracts isolated from tumor necrosis factor alpha-treated A549 cells demonstrated dose-dependent inhibition of NF-kappa B binding by chromium, cadmium, mercury, zinc, and arsenite. Maximum inhibition of binding occurred when these metals were preincubated with the nuclear proteins prior to addition of radiolabeled oligonucleotide. The potency of mercury, cadmium, and zinc for inhibiting binding closely correlated to the affinity of these metals for protein thiols. Further addition of dithiothreitol competitively blocked the effects of all of the metals, except chromium(III), on NF-kappa B binding. This study demonstrates mechanisms for metals to inhibit NF-kappa B-DNA binding through interactions with critical protein sulfhydryls.

Arsenites↗