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Absorption of the biomimetic chromium cation triaqua-mu3-oxo-mu-hexapropionatotrichromium(III) in rats.

The cation [Cr3O(O2CCH2CH3)6(H2O)3]+ has been shown in vitro to mimic to the oligopeptide chromodulin's ability to stimulate the tyrosine kinase activity of insulin receptor and shown in healthy and type 2 diabetic model rats to increase insulin sensitivity and decrease plasma total and low-density lipoprotein cholesterol and triglycerides concentrations. However, the degree to which the complex is absorbed after gavage administration to rats had not been previously determined. The biomimetic cation at nutritional supplement levels is absorbed with greater than 60% efficiency, and at pharmacological levels, it is absorbed with greater than 40% efficiency, an order of magnitude greater absorption than that of CrCl3, Cr nicotinate, or Cr picolinate, currently marketed nutritional supplements. The difference in degree of absorption is readily explained by the stability and solubility of the cation.

Animals↗

Chromium incorporated in RNA and DNA.

The objective of this study was to examine the effect of Cr(III) (chromium chloride) and Cr(VI) (potassium dichromate) on RNA and DNA-chromium adducts formation in isolated nucleic acids and isolated pig lymphocytes. The incubation of cells with potassium dichromate and chromium chloride at concentrations of 10 and 100 microM results in binding of a 1.2-1.9 fold greater number of chromium atoms to nuclear DNA than to total cellular RNA. The incubation of total cellular RNA and nuclear DNA isolated from lymphocytes with CrCl3 and K2Cr2O7 yielded a binding of 1.1-1.6 fold more of Cr atoms to RNA than to DNA. The number of chromium atoms bound to nucleic acids is higher after incubation with K2Cr2O7 than with CrCl3 in both experimental systems.

Animals↗

Treated wood preservatives linked to aquatic damage, human illness, and death--a societal problem.

On February 12, 2002, the US Environmental Protection Agency (EPA) announced a voluntary decision by industry to move consumer use of treated lumber products away from a variety of pressure-treated wood that contains arsenate (As) by December 31, 2003, in favor of new alternative wood preservatives. Chromated copper arsenate (CCA) is a chemical mixture consisting of three pesticidal compounds (As, chromium, and copper) registered for wood preservative uses. CCA is injected into wood by a process that uses high pressure to saturate wood products with the chemical. Only people who have received the proper safety training should use CCA to treat wood products. Around the home, CCA-treated wood is commonly used for decks, walkways, fences, gazebos, boat docks, and playground equipment. Other common uses of CCA-treated wood include highway noise barriers, sign posts, utility posts, and retaining walls. As of January 1, 2004, the EPA is no longer allowing CCA products to be used to treat wood intended for any of these residential uses. This decision will facilitate the voluntary transition to new alternative wood preservatives that do not contain As in both the manufacturing and retail sectors. To its credit, the EPA has developed consumer safety information sheets, hanging signs, end signs, and bin stickers that provide comprehensive information about the dangers of CCA-treated wood, use-site, and handling precautions. The EPA has not concluded that CCA-treated wood poses any unreasonable risk to the public or the environment. Nevertheless, As is a known human carcinogen and, thus, the EPA believes that any reduction in the levels of potential exposure to As is desirable. The toxicologic manifestations have been primarily related to the effects of As exposure from drinking water sources and include the following: acute poisoning incidents, cardiovascular effects, diabetes mellitus, and cancer. Understanding the biomethylation of As is central to elucidating its action as a toxin and a carcinogen. In humans as in many other species, inorganic As is enzymatically converted to the methylated products methyl As (MAs) and dimethyl As (DMAs). The aforementioned voluntary agreement to reduce the uses of CCA-treated wood does not include a ban on the use of CCA for residential roofing. A major reason that this wood product should be banned from residential roofing is that it does not provide a Class "A" fire-rated roof system, which markedly reduce the frequency of residential roof fires.

Arsenic Poisoning↗

Role of thromboxane A2, endothelin-1 and endothelin-3 in rat nephrotoxic serum nephritis.

To clarify the role of thromboxane A2 (TxA2), endothelin-1 (ET-1) and endothelin-3 (ET-3) in the progression of glomerular injury in accelerated nephrotoxic serum nephritis (NTN) in the rat, we studied the expression of ET-1 and ET-3 at the kidney by immunohistochemical method and examined the effect of a novel TxA2 receptor antagonist, S-1452. The S-1452-treated group showed significantly lowered 24-hr proteinuria and milder glomerular cell proliferation and lobulation than the non-treated group (NT group) on experimental day 10. There was no significant difference in the glomerular polymorphonuclear cell (PMN) exudation between the 2 groups. Immunofluorescent findings revealed that ET-1 and ET-3 were seen along the glomerular capillary wall and partly in the mesangial area in all rats of the NTN group. The degree and positive rate of ET-1 and ET-3 staining were significantly higher in the NTN group than in the S-1452 group. These findings suggest that TxA2 may be an important mediator in the development of NTN, and that TxA2 receptor antagonist may be useful for the reduction of glomerular injury in this type of nephritis. In addition, local production of ET may contribute to the development of this nephritis.

Animals↗

Mutagenic effects of chromium trioxide on root tip cells of Vicia faba.

In this study on the mutagenic effects of different concentrations of chromium trioxide (CrO(3)) on Vicia faba root tip, micronucleus assay and chromosome aberration assay were used to determine the mitotic indexes, micronucleus aberration rate and chromosome aberration rate of Vicia faba root tip cells. The results showed that the effects of CrO(3) concentration on the mitotic indexes were complicated. CrO(3) increases the micronucleus aberration rate of Vicia faba root tip cells. It was found that within certain range of CrO(3) concentration the micronucleus aberration rate increased systematically with increased concentration of CrO(3), but that the micronucleus aberration rate decreased at higher level of CrO(3) and that CrO(3) also caused various types of chromosome aberration at a rate which increased systematically with increased concentration of CrO(3). We concluded that CrO(3) has significant mutagenic effect on Vicia faba root tip cells.

Cells, Cultured↗

Joint effects of microwave and chromium trioxide on root tip cells of Vicia faba.

The mutagenic effects of microwave and chromium trioxide (CrO(3)) on Vicia faba root tip were studied. Micronucleus assay and chromosomal aberration assay were used to determine the mitotic index, the micronucleus frequency and chromosomal aberration frequency of Vicia faba root tip cells induced by microwave and CrO(3). The results showed that the micronucleus frequency decreased, and that the mitotic index and chromosomal aberration frequency showed linear dose responses to CrO(3), in treatment of microwave for 5 s. In microwave of 25 s, the mitotic index decreased, the micronucleus frequency and chromosomal aberration frequency increased with increase of CrO(3) concentration. We concluded that microwave and CrO(3) had antagonistic effect on the mitotic index of Vicia faba root tip cells, but had synergetic effect on micronucleus frequency and chromosomal aberration frequency of Vicia faba root tip cells.

Cells, Cultured↗

Synoviorthesis with colloidal 32P chromic phosphate for the treatment of hemophilic arthropathy.

Between 1977 and 1992, we performed ninety-two synoviortheses (destruction of synovial tissue by intra-articular injection of a radioactive agent) on forty-eight patients who had a severe congenital disorder of hemostasis and chronic hemophilic synovitis that was resistant to conventional treatment. Colloidal 32P chromic phosphate was injected intra-articularly: 1.0 millicurie for knees and 0.5 millicurie for other joints. The duration of follow-up ranged from one to fifteen years. The frequency and importance of bleeding decreased in most of the patients. The range of motion of half of the joints remained stable or improved and that of the other half continued to decrease. Radiographic scores worsened progressively despite the decreased frequency of hemarthrosis. In most patients, the extra-articular leakage of the radioactive agent was slight. Chromosome breakages were observed almost exclusively in patients who were seropositive for human immunodeficiency virus and in whom the CD4-lymphocyte count was decreased from normal. The patients' level of satisfaction with the results was high.

Adolescent↗

Evaluation of intestinal permeability and gluten sensitivity in Soft-Coated Wheaten Terriers with familial protein-losing enteropathy, protein-losing nephropathy, or both.

OBJECTIVE: To evaluate intestinal permeability and gluten sensitivity in a family of Soft-Coated Wheaten Terriers (SCWT) affected with protein-losing enteropathy (PLE), protein-losing nephropathy (PLN), or both. ANIMALS: 6 affected adult dogs. PROCEDURE: Intestinal biopsy specimens, urine protein-to-creatinine ratio, serum concentrations of albumin and globulin, and concentration of alpha1-protease inhibitor in feces were evaluated before, during, and 13 weeks after daily administration of 10 g of gluten for 7 weeks. Eosinophils and lymphocytes-plasmacytes were enumerated in intestinal biopsy specimens. Intestinal permeability was evaluated before and during the sixth week of gluten administration via cellobiose-mannitol and chromium-EDTA absorption tests. RESULTS: Serum globulin concentration decreased significantly after prolonged administration of gluten. Although not significant, there was an increase in lymphocytes-plasmacytes and a decrease in eosinophils in intestinal biopsy specimens. Furthermore, these counts were greater than those reported for clinically normal dogs. Gluten administration did not increase intestinal permeability. CONCLUSIONS AND CLINICAL RELEVANCE: Daily administration of gluten was associated with a significant decrease in serum globulin concentration in SCWT affected with PLE or PLN, but other variables remained unchanged. Although enhanced wheat-gluten sensitivity may be one factor involved in the pathogenesis of PLE or PLN in SCWT, this syndrome does not appear to be the result of a specific sensitivity to gluten.

Animals↗

Hexavalent chromium responsible for lung lesions induced by intratracheal instillation of chromium fumes in rats.

Lung toxicity of chromium fumes (Cr fumes) was examined by a single intratracheal instillation into rats of 10.6 mg and 21.3 mg Cr fumes/kg body weight and by repeated (3 times) instillations of 10.8 mg and 21.7 mg Cr fumes/kg. The pathological changes were compared with those induced by single administrations of 3.2 mg and 19.2 mg Na2CO3 solution-insoluble fraction of Cr fumes (Cr-Fr)/kg and 20.8 mg commercially available chromium (III) oxide powder (Cr (III) oxide)/kg. Single and repeated administrations of Cr fumes suppressed growth rate in a dose-dependent manner, but administrations of Cr-Fr and Cr (III) oxide did not. A single administration of Cr fumes produced granulomas in the entire airways and alveoli with progressive fibrotic changes, as well as severe mobilization and destruction of macrophages and foamy cells. Those histopathological changes were aggravated by the repeated administration of Cr fumes. On the other hand, single administrations of Cr-Fr and Cr (III) oxide produced no remarkable histopathological changes. Cr fumes were found to be composed of 73.5% chromium (III) oxide and 26.5% chromium (VI) oxide. The primary particles of Cr fumes and Cr-Fr were similar, 0.02 micron in size (sigma g: 1.25), and Cr (III) oxide particles were 0.30 micron in size (sigma g: 1.53), measured by analytical electron microscopy (ATEM). Diffuse clusters of the primary particles in Cr fumes were identified as Cr (VI) oxide. The present results suggested that the lung toxicity of Cr fumes was mainly caused by these Cr (VI) oxide (CrO3) particles in Cr fumes.

Administration, Inhalation↗

Effect of level of intake and supplemental barley on marker estimates of fecal output using an intraruminal continuous-release chromic oxide bolus.

Sixty wethers (average BW = 45 kg) fitted with fecal collection bags were used in four experiments to evaluate the ability of a intraruminal continuous-release chromic oxide bolus to predict fecal DM output. In Exp. 1, 18 wethers housed in metabolism crates were fed barley at either 0, 100, or 200g/d and allowed ad libitum consumption of alfalfa pellets. In Exp. 2, 18 wethers were housed in metabolism crates and fed alfalfa pellets at either 70, 85, or 125% of pre-study ad libitum consumption. In Exp. 3, 12 wethers grazed a sagebrush-bunchgrass range and were individually fed barley at 0 or 200 g/d. In Exp. 4, 12 wethers grazed either an ungrazed (383 kg/ha herbaceous biomass) or a heavily grazed (175 kg/ha herbaceous biomass) sagebrush-bunchgrass range. Experiments 1 and 2 were balanced 3 x 3 Latin squares, and Exp. 3 and 4 were crossover designs. Chromium content was determined in rectal grab samples. Treatment effects were compared using marker-estimated fecal output divided by total fecal collection, multiplied by 100, as the dependent variable. Accuracy of the estimate was verified by comparing marker-estimated fecal output with total fecal collection using a paired t-test. In Exp. 1 and 2, treatments were different (P less than .05). No differences (P greater than .50) were detected in Exp. 3 and 4. In Exp. 1, 2, and 3 accuracy was different (P less than .02) among wethers within study and treatment. Only in Study 4 were minor or no differences (P greater than .09) in accuracy found.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Evaluation of the Captec chrome controlled-release device for the estimation of fecal output by grazing sheep.

Three grazing experiments were conducted to compare actual fecal output (FO) by sheep, determined with fecal collection bags, to fecal output predicted using Captec chromic oxide (Cr2O3) controlled-release capsules. In Exp. 1, 14 crossbred wethers dosed with controlled-release Cr2O3 capsules rotationally grazed four paddocks of alfalfa (Medicago sativa L.) for 18 d. Total fecal collection and grab samples were taken daily from each animal; feces were dried and assayed for Cr. From d 5 to 12 after dosing, mean actual FO (429 +/- 9.6 g of DM/d) differed (P less than .001) from FO predicted by the capsule (463 +/- 12.8 g of DM/d). The correlation between actual and predicted FO was r = .59. When data were averaged by day, the correlation increased to .82. In Exp. 2, Tifton 44 bermudagrass (Cynodon dactylon [L.] Pers.) was strip-grazed for 30 d by the same 14 wethers used in Exp. 1. Mean actual FO (369 +/- 5.1 g of DM/d) differed (P less than .0001) from predicted FO (415 +/- 9.3 g of DM/d), with a correlation of .60. In Exp. 3, 72 crossbred lambs were blocked by weight (light and heavy) and assigned to six groups of eight wethers (four with fecal bags) and four ewes, allotted randomly to three stocking rates (74, 99, and 148 sheep/ha). Sampling occurred from d 6 to 10 after dosing (Period 1) and d 20 to 24 after dosing (Period 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Evaluation of the Captec controlled-release chromic oxide capsule for fecal output determination in sheep.

One pen feeding study was conducted with 24 wether lambs to compared fecal output (FO) determined by total fecal collection with FO estimated by dosing lambs with chromic oxide controlled-release capsules. Lambs (39 +/- 1.5 kg BW) were fed either alfalfa hay (ALF), Coastal bermudagrass hay (CBG), or a commercially available pelleted (PEL) sheep diet (eight lambs/diet). After dosing, rectal grab samples and total collection of feces were taken daily for 31 d. Constant fecal excretion of Cr was achieved approximately on d 8 (range = d 5 to 13) after dosing. Capsule expiration was accompanied by a sharp peak in Cr excretion approximately on d 27 (range = d 24 to 30). Complete excretion of Cr by d 31 occurred in only seven lambs. Agreement between actual and predicted FO was examined by linear regression from d 8 to 22. Best parameter estimates and highest R2 were observed when sampling a) every other day from d 11 to 19 (five samplings), b) daily from d 8 to 17, c) daily during the entire period, and d) daily from d 13 to 22. Sampling for 5 d chosen at random consistently gave poor results. Sampling every 3rd d gave the poorest results. Controlled-release capsules predicted FO very accurately in lambs fed ALF. Reliable estimates were obtained in 67% of cases investigated with CBG, whereas only 25% of estimates were reliable with PEL. The controlled-release capsules always overestimated FO of wethers fed CBG and PEL, implying that in those lambs the actual release rate of Cr was less than that specified by the manufacturer.

Animals↗