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The effects of potassium bichromate, benzene, and their mixture on cell immunological parameters and the blood content of trace elements were studied in Wistar rats. Oral administration of benzene, potassium bichromate, and their mixture to Wistar rats was found to result in reductions in cell immunological parameters (the count of leukocytes, thymocytes, splenocytes, myelokaryocytes, the level of phagocytic indices) and the levels of copper, iron, nickel, and, on the contrary, increases in the concentrations of zinc and chromium in blood.

This study was conducted to evaluate the effects of chromium nanoparticles (CrNano) on the hormone and immune responses of rats in heat stress condition. A total of 80 male Sprague-Dawley rats were randomly assigned to four dietary treatment groups (n = 20). The first group was offered a basal diet as a control. The second, third, and fourth groups received basal diet supplemented with 150, 300, and 450 microg/kg Cr, respectively, in the form of CrNano. At the end of the 8-week trial, growth performance, food utilization, and sera concentrations of hormones, immunoglobulins, and alexins were determined. Lymphocyte proliferation activity, antibody response to injected sheep red blood cells (SRBCs), and phagocytosis of peritoneal macrophages were determined by (3)H-thymidine uptake method, plaque-forming cells (PFC) assay, and ingesting chicken red blood cells test, respectively. The results indicated that rats that received CrNano exhibited no changes in growth rate and food efficiency compared to the control group. However, dietary supplementation of 150, 300, and 450 microg/kg Cr from CrNano significantly decreased serum concentrations of insulin and cortisol, increased sera levels of insulin-like growth factor I and immunoglobulin G, and enhanced the lymphoproliferative response, anti-SRBC PFC response, and phagocytic activity of peritoneal macrophages. These results suggest that dietary supplementation of Cr as CrNano affects hormone and immune status in heat-stressed rats.

Background: Hexavalent chromium [Cr(VI)] is a human carcinogen after inhalation exposure. Humans also ingest Cr(VI) from contaminated drinking water and soil; however, limited data exist on the oral toxicity and carcinogenicity of Cr(VI)., Objective: We characterized the chronic oral toxicity and carcinogenicity of Cr(VI) in rodents., Methods: The National Toxicology Program (NTP) conducted 2-year drinking water studies of Cr(VI) (as sodium dichromate dihydrate) in male and female F344/N rats and B6C3F1 mice., Results: Cr(VI) exposure resulted in increased incidences of rare neoplasms of the squamous epithelium that lines the oral cavity (oral mucosa and tongue) in male and female rats, and of the epithelium lining the small intestine in male and female mice. Cr(VI) exposure did not affect survival but resulted in reduced mean body weights and water consumption, due at least in part to poor palatability of the dosed water. Cr(VI) exposure resulted in transient microcytic hypochromic anemia in rats and microcytosis in mice. Nonneoplastic lesions included diffuse epithelial hyperplasia in the duodenum and jejunum of mice and histiocytic cell infiltration in the duodenum, liver, and mesenteric and pancreatic lymph nodes of rats and mice., Conclusions: Cr(VI) was carcinogenic after administration in drinking water to male and female rats and mice.

Certain particulate hexavalent chromium [Cr(VI)] compounds are human respiratory carcinogens that release genotoxic soluble chromate, and are associated with fibrosis, fibrosarcomas, adenocarcinomas and squamous cell carcinomas of the lung. We postulate that inflammatory processes and mediators may contribute to the etiology of Cr(VI) carcinogenesis, however the immediate (0-24 h) pathologic injury and immune responses after exposure to particulate chromates have not been adequately investigated. Our aim was to determine the nature of the lung injury, inflammatory response, and survival signaling responses following intranasal exposure of BALB/c mice to particulate basic zinc chromate. Factors associated with lung injury, inflammation and survival signaling were measured in airway lavage fluid and in lung tissue. A single chromate exposure induced an acute immune response in the lung, characterized by a rapid and significant increase in IL-6 and GRO-alpha levels, an influx of neutrophils, and a decline in macrophages in lung airways. Histological examination of lung tissue in animals challenged with a single chromate exposure revealed an increase in bronchiolar cell apoptosis and mucosal injury. Furthermore, chromate exposure induced injury and inflammation that progressed to alveolar and interstitial pneumonitis. Finally, a single Cr(VI) challenge resulted in a rapid and persistent increase in the number of airways immunoreactive for phosphorylation of the survival signaling protein Akt, on serine 473. These data illustrate that chromate induces both survival signaling and an inflammatory response in the lung, which we postulate may contribute to early oncogenesis.

Chromium is a widespread industrial compound. The soluble hexavalent chromium Cr (VI) is an environmental contaminant widely recognized as carcinogen, mutagen, and teratogen toward humans and animals. The fate of chromium in the environment is dependent on its oxidation state. The reduction of Cr (VI) to Cr (III) results in the formation of reactive intermediates leading to oxidative tissue damage and cellular injury. In the present investigation, Potassium dichromate was given intraperitoneally to Sprague-Dawley rats for 5 days with the doses of 2.5, 5.0, 7.5, and 10 mg/kg body weight per day. Oxidative stress including the level of reactive oxygen species (ROS), the extent of lipid peroxidation and the activity of antioxidant enzymes in both liver and kidney was determined. DNA damage in peripheral blood lymphocytes was determined by single-cell gel electrophoresis (comet assay). The results indicated that administration of Cr (VI) had caused a significant increase of ROS level in both liver and kidney after 5 days of exposure, accompanied with a dose-dependent increase in superoxide dismutase and catalase activities. The malondialdehyde content in liver and kidney was elevated as compared with the control animals. Dose- and time-dependent effects were observed on DNA damage after 24, 48, 72, and 96 h posttreatment. The results obtained from the present study showed that Cr (VI) could induce dose- and time-dependent effects on DNA damage, both liver and kidney show defense against chromium-induced oxidative stress by enhancing their antioxidant enzyme activity. However, liver was found to exhibit more antioxidant defense than the kidney.

This study was designed to investigate the effects of supplementation and deficiency of dietary chromium (Cr), zinc (Zn) and combination of zinc and chromium on lipid peroxidation and antioxidant enzymes. A total of 84 male Wistar albino rats were fed rat chow containing different levels of Zn and Cr throughout the 84 days. Blood samples were collected for analysis of Thiobarbituric acid reactive substances (TBARS), Superoxide dismutase (SOD), Catalase (CAT) and Glutathione peroxidase (GSH-Px). TBARS concentrations in rats fed high-Cr diet, high-Zn and Cr diet and low-Zn diet were significantly higher than those determined in the control group (p < or = 0.05). CAT activities in rats fed high-Cr diet were significantly higher than those observed in the control group. Cu-Zn SOD and GSH-Px activities were significantly higher in rats fed high-Cr diet, high-Zn and Cr diet, low-Zn diet, and low-Zn and Cr diet when compared to the activities found in the controls. These results suggest that trivalent chromium supplementation increase antioxidant enzymes by enhancement of lipid peroxidation, but Zn supplementation does not have any effect on lipid peroxidation. Also Zn deficiency resulted in increased lipid peroxidation, SOD and GSH-Px activities because of the oxidative stress caused by zinc deficiency.

The concentration of Cr in several tissues in response to high-level, short-term supplementation was used to determine the relative bioavailability among 4 organic Cr sources and to assess the relative safety of high levels of supplementation. Crossbred pigs (n = 40; mean BW = 48.1 +/- 0.9 kg) were allotted to 5 diets: a control diet with no added Cr, or 5,000 microg/kg of Cr from Cr tripicolinate (CrTP), Cr propionate (CrPrp), Cr methionine (CrMet), or Cr yeast (CrY). Twenty gilts were housed individually and barrows were housed in pairs. Average duration of feeding before slaughter was 75 d. For the total experiment, pigs fed the unsupplemented diet had less ADG than pigs fed CrY (P < 0.05). Serum clinical chemistry values, obtained during the final week of the experiment, demonstrated few effects with no responses that would raise concern about metabolic changes in response to the Cr sources. The effects of the forms of Cr fed on carcass measurements and meat quality were also minimal. All Cr sources reduced cooler shrink (P < 0.05) and most resulted in some meat color change on d 1 postslaughter. For tissue Cr content, 4 of 5 tissues (bone, kidney, liver, and ovary) were increased (P < 0.05) in Cr content by supplementation with CrTP and CrMet, whereas only 2 tissues (bone and kidney) were increased (P < 0.05) by CrY, and none were increased by CrPrp. In all tissues of response, CrTP exceeded CrMet and CrMet exceeded CrY. Comparing the relative increase in tissue Cr for all responsive tissues (bone, kidney, liver, and ovary) gave a range of responses, for which the mean bioavailability relative to CrTP across tissues was 13.1% for CrPrp (0.2 to 19.0%), 50.5% for CrMet (36.2 to 79.1%), and 22.8% for CrY (2.5 to 47.9%). In summation, these results show very clear Cr effects on multiple tissues, which is conclusive evidence of absorption and deposition. The lack of a negative response in growth performance, carcass measures, and clinical chemistry at the increased quantities used herein provides assurance that normal quantities of addition are extremely safe.

Hexavalent chromium (Cr-VI) is used in a wide range of industries. Cr-VI from chromate industries and atmospheric emissions contribute to the Cr contamination in the environment. Cr is a reproductive metal toxicant that can traverse the placental barrier and cause a wide range of fetal effects including ovotoxicity. Therefore, the goal of this study was to investigate the basic mechanisms involved in Cr(VI)-induced ovotoxicity, and the protective role of vitamin C on ovarian follicular development and function in Cr(VI)-induced reproductive toxicity using both in vivo and in vitro approaches. Lactating rats received potassium dichromate (200 mg/L) with or without vitamin C (500 mg/L), through drinking water from postpartum days 1-21. During postnatal days (PND) 1-21 the pups received Cr(VI) via the mother's milk. Pups from both control and treatment groups were continued on regular diet and water from PND-21 onwards, and euthanized on PND-21, -45 and -65. Cr(VI) decreased steroidogenesis, GH and PRL, increased FSH and did not alter LH. Cr(VI) delayed puberty, decreased follicle number, and extended estrous cycle. Spontaneously immortalized rat granulosa cells were treated with 12.5 microM (IC(50)) potassium dichromate for 12 and 24 h, with or without vitamin C pre-treatment. Cr(VI) decreased the mRNA expressions of StAR, SF-1, 17beta-HSD-1, 17beta-HSD-2, FSHR, LHR, ER alpha and ER beta. Vitamin C pre-treatment protected ovary and granulosa cells from the deleterious effects of Cr(VI) toxicity, both in vivo and in vitro. Therefore, Cr(VI) toxicity could be a potential risk to the reproductive system in developing females, and vitamin C plays a protective role against Cr(VI)-induced ovotoxicity.

In patients with orthopaedic implants, metallic particles have been shown to be disseminated widely throughout the body, particularly in the liver, spleen and lymph nodes. Levels of metal particles and ions in distant organs were highest in patients with loose, corroded prostheses, and when stainless steel and cobalt chrome alloy corrode, chromium is released predominantly as Cr (VI), a toxic ion. This manuscript investigates the interaction of Cr (VI) with liver cells in terms of inhibition of macromolecular synthesis, and the contribution of reduced glutathione (GSH), DT-diaphorase and glutathione reductase (GRd) to the toxicity of Cr (VI). Cr (VI) caused concentration dependent inhibition of protein, DNA and RNA synthesis in hepatocytes. GRd and to a lesser extent DT-diaphorase activities were involved in the generation of toxic intermediates. GRd activity was markedly inhibited during the reduction of Cr (VI), and GSH levels decreased. The concentrations of Cr (VI) found to inhibit macromolecular syntheses in this study are clinically relevant: it is therefore important to develop implants with minimum wear potential.

Intake of chromium was estimated using a duplicate diet sampling method of 108 meals (36 breakfasts, 36 lunches and 36 dinners) from the restaurant of the Hospital of Motril (S.E. Spain), corresponding to 36 consecutive days. Total and dialyzable Cr levels were measured by a validated electro-thermal atomic absorption spectrometry (ETAAS) method. A mean Cr fraction of 26 +/- 12 microg meal (-1) was found. The Cr uptake from meals was directly and significantly (p < 0.001) correlated with their macronutrient (carbohydrates, fibre and protein) content. Cereals and cereal by-products, legumes, dry fruits, meat, potatoes, dairy products and seafood are the primary sources of Cr. The mean Cr fraction dialyzed through dialysis tubing was 1.2 +/- 1.1 microg meal(-1) (4.6 +/- 3.8% as mean Cr dialysability). Cr intake for breakfasts was significantly lower (p < 0.001). A correlation between the logarithmic data of total and dialyzable fraction of Cr in meals (p = 0.020) was found and dialysis ratio enhancement and, therefore, bioavailability increased with total Cr. The dialysed element content present in meals was significantly correlated with fibre, protein, Fe, Na, I, F, sodium, ascorbic acid and vitamin A levels (p < 0.05). At Fe contents in meals higher than congruent with7.5 mg meal(-1) the net absorption of Cr decreased significantly. The mean Cr daily dietary intake (DDI) was 77 +/- 17 microg day (-1) which indicates that no adverse effects in relation to Cr nutrition (deficiency or toxicity) should occur in individuals from the area.

Holstein cows (n = 72) entering second or later lactation were used to determine whether metabolic indices and hepatic capacities for oxidation and gluconeogenesis from propionate are affected by source of carbohydrate in the prepartum diet and chromium-l-methionine (Cr-Met) supplementation throughout the periparturient period. Cows were fed prepartum diets as total mixed rations with the concentrate portion based either on starch-based cereals [high nonfiber carbohydrate (NFC); 1.59 Mcal/kg of net energy for lactation (NE(L)), 14.4% crude protein (CP), 40.3% NFC] or nonforage fiber sources (low NFC; 1.54 Mcal/kg of NE(L), 14.5% CP, 33.6% NFC) from 21 d before expected parturition until parturition. After parturition all cows were fed a common lactation total mixed ration (1.74 Mcal/kg of NE(L), 16.5% CP, 40.0% NFC). The Cr-Met was supplemented once daily via gelatin capsule at dosages of 0, 0.03, or 0.06 mg of Cr/kg of BW(0.75). Thus, treatments were in a 2 (carbohydrate source) x 3 (Cr-Met) factorial arrangement. There was no effect of prepartum carbohydrate source on pre- and postpartum plasma concentrations of glucose, nonesterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), insulin, glucagon, or insulin to glucagon ratio. However, cows fed the low NFC diet during the prepartum period tended to have greater plasma NEFA and lower BHBA concentrations postpartum. Liver glycogen concentrations tended to be greater on d 1 postpartum for cows fed low NFC prepartum. Supplementing 0.03 mg/kg of BW(0.75) of Cr as Cr-Met increased prepartum plasma glucose and glucagon concentrations and tended to decrease prepartum plasma NEFA concentrations compared with either 0 or 0.06 mg of Cr/kg of BW(0.75). Postpartum plasma glucose concentrations decreased linearly and glucagon concentrations were increased quadratically by administering increasing amounts of Cr-Met. Supplementing Cr-Met did not affect prepartum plasma concentrations of insulin or BHBA, postpartum NEFA or BHBA, or liver composition. There was an interaction of prepartum carbohydrate source and Cr-Met supplementation such that in vitro hepatic conversion of [1-(14)C]propionate to both CO(2) and glucose was similar or increased when Cr-Met was supplemented to cows fed the low NFC diet but decreased when Cr-Met was supplemented to cows fed the high NFC diet. Insulin addition in vitro did not affect hepatic metabolism of propionate on d 1 postpartum. Overall, both the NFC content of the prepartum diet and Cr-Met had only modest effects on metabolic indices in this experiment.

Ruminal administration of a triple indigestible marker system comprised of cobalt EDTA (CoEDTA), ytterbium acetate (YbAc), and chromium-mordanted straw (CrS) decreases product:substrate ratios for Delta9-desaturase in bovine milk fat. This experiment was designed to identify the marker(s) responsible and develop an alternative system for simultaneous determination of nutrient flow in the gastro-intestinal tract and milk fatty acid composition. Five lactating dairy cows were used in a 5 x 5 Latin square with 21-d periods to evaluate the effects of YbAc, CoEDTA, and CrS independently or as part of a triple marker system (TMS), and CrEDTA as an alternative to CoEDTA on milk fat composition. Markers were administered in the rumen over a 7-d interval and samples of milk were collected on d -1, 3, 7, and 11. Both TMS and CoEDTA alone reduced the concentrations of milk fatty acids containing a cis-9 double bond, whereas YbAc, CrS, and CrEDTA had no effect. Reductions in product:substrate ratios for Delta9-desaturase were time dependent and evident within 3 d of administration. Ruminal infusion of CoEDTA for 7 d induced mean decreases in milk cis-9 14:1/14:0, cis-9 16:1/16:0, cis-9 18:1/18:0, and cis-9, trans-11 conjugated linoleic acid/trans-11 18:1 concentration ratios of 47.7, 26.7, 40.3, and 42.6%, respectively. In conclusion, ruminal infusion of CoEDTA alters milk fatty acid composition and appears to inhibit Delta9-desaturase activity in the bovine mammary gland. Results indicate that a TMS based on CrEDTA, YbAc, and indigestible neutral detergent fiber can be used for estimating nutrient flow without altering milk fat composition in lactating cows.

1. The study was conducted to ascertain the effects of supplemental organic acids and chromium (Cr) on production and carcase traits of broiler chickens. 2. A total of 120 1-d-old broiler chicks were divided into 4 treatment groups in a 2 x 2 factorial design (each treatment group contained 6 replicates with 5 birds per replicate). 3. The diets were supplemented with an organic acid blend containing ortho-phosphoric, formic and propionic acid and calcium propionate (1 g/kg diet) and inorganic trivalent chromium (Cr(3+)) as chromic chloride hexahydrate (0.5 mg/kg diet) either independently or together as a combination for 35 d. 4. Individual supplementation of organic acids and Cr(3+) and their combination significantly improved the food conversion ratio, hot and dressed carcase weight and weight of the wholesale cuts compared to the control group of birds. 5. Organic acids, either independently or along with Cr(3+), increased total accretion of ash in carcase. Protein accretion was improved by dietary Cr(3+) and organic acid supplementation compared to the control group and a further improvement in this regard was observed when Cr(3+) and organic acid were supplemented together. Across the treatment groups meat fat content and fat accretion were lower in birds receiving dietary Cr(3+) supplementation. 6. Circulatory Cr(3+) and meat Cr(3+) concentration increased compared to the other treatment groups when Cr(3+) was supplemented to the birds. 7. It was concluded that, instead of individual supplementation, a combination of Cr(3+) and organic acids may improve the production and carcase traits of broilers more effectively presumably because of an additive effect.

To establish the potential use of cell cultures as a simple and sensitive biological tool to detect environmental pollutants, six cell lines established from several fish species including GCF (grass carp fins), CIK (Ctenopharyngodon idellus kidney), EPC (epithelioma papulosum cyprini), CCO (channel catfish ovary), BB (brown bullhead caudal trunk) and FHM (fathead minnow muscle) were tested and compared for their cytotoxic sensitivity to four heavy metals: cadmium (Cd), chromium (Cr), zinc (Zn), and copper (Cu). Following a 24-h exposure to these metal salts at selected concentrations, test cells were characterized by morphology, viability and proliferation. Our results indicate that all these metal salts are cytotoxic to these fish cell lines, but at varied levels. Calculated inhibitory concentration (IC(50)) values revealed that the cytotoxicity of Cr and Cd was significantly more pronounced than that of the other two metal salts. Comparative analysis of these fish cell lines showed that C. idellus kidney (CIK) cells are the most sensitive cell line to copper, epithelioma papulosum cyprini (EPC) cells are more sensitive than other cells to Cr and Zn, while channel catfish ovary (CCO) cell line is the most sensitive one to Cd. In conclusion, CIK, EPC and CCO could potentially be sensitive bio-indicators for the initial monitoring and assessment of acute cytotoxicity of heavy metals in the aquatic environment.

Algal bloom with consequent production of marine toxins contaminating bivalves is increasing in costal regions worldwide because of sea water quality worsening. Contamination of seafood by diarrheic shellfish poisoning toxins (DSP) together with metals is frequently reported, a phenomenon not fully explained yet. In this context, metal ions were assayed in clams collected from the banned area of Boughrara, Tunisia, contaminated by Gymnodinium and other algae such as Dinophysis sp, accumulated by these bivalves. The presence of toxic metals ions such as Chromium (Cr) and Cadmium (Cd) in meat, shells, and water released by the clams prompted us to experiment in Caco-2 intestinal cell line toxic effects of these heavy metals ions in combination with okadaic acid, one DSP present in clams to assess the potential global toxicity. Cr and Cd produce additive effects in (i) reactive oxygen species production, (ii) cytotoxicity as assessed by the mitochondrial activity testing method (MTT test), and (iii) DNA lesions evaluated by agarose gel electrophoresis and acridine orange staining. Exaggerated DNA fragmentation is observed, suggesting an overloading of repair capacity of Caco-2 cells. The apoptosis suggested by a DNA fragment sizing (180-200 bp) in agarose gel and mechanisms underlying these additive effects in Caco-2 cells still need to be more comprehensively explained.

Objectives: To assess the variable concentrations of several metal salts on human oligodendrocyte MO3.13 and human gingival fibroblasts HGF and to enable any difference in cell type sensitivity to be examined., Methods: Cytotoxicity was measured as mitochondrial dehydrogenase activity assessed by MTT assay. The mean of the 50% response (TC50) was calculated by using equation-fitting software (TableCurve 2D)., Results: The results of the MTT assay showed that metal ions induce reproducible cytotoxic effects in MO3.13 oligodendroglia and human gingival fibroblasts, that is dose dependent on the tested agent. Cadmium relatively showed the highest cytotoxic effects on MO3.13 cells (TC50 9.8 microM) whereas mercury showed the highest cytotoxic effects on HGF (TC50 74 microM) comparing with other tested metals. The two cell types responded differently. MO3.13 cells were more sensitive than the HGF to most of the metals., Conclusion: Metals have a wide range of toxicity to human oligodendroglial cells (MO3.13) and human gingival fibroblasts. Fortunately, however, in vivo the normal levels of these metals are much lower than those determined as toxic in vitro.

Trivalent chromium [Cr(III)] is recognized as an essential nutrient, and is widely used as a nutritional supplement for humans and animals. Recent reports of the induction of genetic damage in cultured cells exposed to Cr(III) compounds in vitro have heightened the concern that Cr(III) compounds may exert genotoxic effects under certain conditions, raising the question of the relative benefit versus risk of dietary and feed supplementation practices. We have reviewed the literature since 1990 on genotoxic effects of Cr(III) compounds to determine whether recent findings provide a sufficient weight of evidence to modify the conclusions about the safety of this dietary supplement reached in the several comprehensive reviews conducted during the period 1990-2004. The extensive literature on genotoxic effects of Cr(III) compounds includes many instances of conflicting information, with both negative and positive findings often reported in similar test systems. Outcomes of in vitro tests conducted with Cr(III) in cultured cells are quite variable regardless of the chemical form of the chromium compound tested. The in vitro data show that Cr(III) has the potential to react with DNA and to cause DNA damage in cell culture systems, but under normal circumstances, restricted access of Cr(III) to cells in vivo limits or prevents genotoxicity in biological systems. The available in vivo evidence suggests that genotoxic effects are very unlikely to occur in humans or animals exposed to nutritional or to moderate recommended supplemental levels of Cr(III). However, excessive intake of Cr(III) supplements does not appear to be warranted at this time. Thus, like other nutrients that have exhibited genotoxic effects in vitro under high exposure conditions, nutritional benefits appear to outweigh the theoretical risk of genotoxic effects in vivo at normal or modestly elevated physiological intake levels.

Intracellular reduction of hexavalent chromium [Cr(VI)] is associated with the production of reactive oxygen species (ROS) and subsequent oxidative damage to different intracellular molecules like DNA, proteins and lipids is believed to contribute to the process of carcinogenesis. Aim of this study was to develop a model to establish a relationship between intracellular and macromolecule-bound chromium and some biomarkers of oxidative stress in two in vitro cell lines. Human lung adenocarcinoma (A549) and human bronchial epithelial (BEAS2B) cells were exposed for 3, 8 and 24 hours to relatively low doses (0.5--1--2 microM) of Cr(VI), i.e., to concentrations similar to what measured and reported by some authors in unexposed subjects and chromate workers. The results show that the differential cytotoxicity of Cr(VI) on the A549 and BEAS2B cell lines may be related both to their different polymorphism of Glutathione S-transferases genes and probably to their unlike permeability to Cr(VI). The glutathione decrease and the induction of HO-1 observed only in BEAS2B cells after Cr(VI) exposure strengthen the idea that glutathione S-transferases activity may accelerate the reduction of Cr(VI) to Cr(III) with the concomitant induction of oxidative stress. In conclusion, the determination of intracellular Cr in cellular models can be considered an important step in comparing in vitro and in vivo models on the basis of target doses and a promising approach to study the effects of pneumotoxic compounds.

Considerable controversy exists regarding the use of chromium (Cr) supplementation to modulate carbohydrate metabolism in subjects with diabetes. Recently, we reported that Cr supplementation, provided as 1000 microg/d as Cr picolinate, enhanced insulin sensitivity in subjects with type 2 diabetes mellitus. Our data agreed with some, but not all, studies that evaluated a similar dose and formulation in type 2 diabetes mellitus and suggested that subject selection and characteristics may be important considerations when assessing the clinical response. Thus, the goal of this study was to assess which metabolic or clinical characteristics, when obtained at baseline, best determine a clinical response to Cr when assessing changes in insulin sensitivity. Seventy-three subjects with type 2 diabetes mellitus were assessed in a double-blinded, randomized, placebo-controlled study. Subjects were assessed at baseline for glycemic control with glycated hemoglobin measures, oral glucose tolerance tests, and body weight and body fat measures (dual-energy x-ray absorptiometry). After baseline, insulin sensitivity in vivo was assessed with the use of hyperinsulinemic-euglycemic clamps. After the baseline clamp, subjects were randomized to receive Cr supplementation (1000 microg Cr/d provided as Cr picolinate) or placebo daily for 6 months. All study parameters were repeated after 6 months. The relationship of the baseline characteristics of the study subjects to the change in insulin sensitivity was determined. Sixty-three percent of the subjects with type 2 diabetes mellitus responded to the Cr treatment as compared with 30% with placebo. The only subject variable significantly associated with the clinical response to Cr was the baseline insulin sensitivity, as assessed with the hyperinsulinemic-euglycemic clamp (partial R(2) = .4038) (P = .0004). Subject phenotype appears to be very important when assessing the clinical response to Cr because baseline insulin sensitivity was found to account for nearly 40% of the variance in the clinical response to Cr.

Objective: A systematic review of the effect of chromium supplementation on glucose metabolism and lipid levels., Research Design and Methods: A literature search was conducted in MEDLINE and the Commonwealth Agricultural Bureau. Eligible studies were English language randomized controlled trials of chromium supplement intake > or = 3 weeks, with > or = 10 participants receiving chromium. All trials with glucose metabolism outcomes and trials of individuals with diabetes or glucose intolerance for lipid outcomes were included. Meta-analyses were performed as appropriate., Results: Forty-one studies met criteria, almost half of which were of poor quality. Among participants with type 2 diabetes, chromium supplementation improved glycosylated hemoglobin levels by -0.6% (95% CI -0.9 to -0.2) and fasting glucose by -1.0 mmol/l (-1.4 to -0.5) but not lipids. There was no benefit in individuals without diabetes. There were some indications of dose effect and differences among chromium formulations. Larger effects were more commonly observed in poor-quality studies. The evidence was limited by poor study quality, heterogeneity in methodology and results, and a lack of consensus on assessment of chromium status., Conclusions: No significant effect of chromium on lipid or glucose metabolism was found in people without diabetes. Chromium supplementation significantly improved glycemia among patients with diabetes. However, future studies that address the limitations in the current evidence are needed before definitive claims can be made about the effect of chromium supplementation.

Trivalent chromium (Cr3+) is an essential trace element involved in insulin function. Cr deficiencies result in decreased insulin sensitivity, glucose intolerance and an increased risk of diabetes. Cr status decreases with age suggesting that the elderly may be at high risk of Cr deficiency. This study aimed to provide information about the Cr content of foods in France and the Cr intake in French free-living elderly. We measured the food Cr content and daily Cr intake of freely chosen diets for 3 d in twelve French free-living elderly people and their Cr excretion and plasma hormonal related variables, leptin, insulin and cortisol. Considering the relationship between insulin resistance and oxidative stress, we also determined plasma thiobarbituric acid reactive substance, thiol groups and total and reduced glutathione. Although these subjects had well-balanced diets, their daily Cr intakes did not reach the French recommendations. The low Cr intakes were due to the low Cr density of the foods. We found a negative correlation between Cr intakes and insulin, BMI and leptin.

This 6-week study was conducted to evaluate the effects of seven different levels of dietary chromium (Cr) (0, 75, 150, 300, 450, 600, and 1 200 ppb Cr) in the form of Cr nanoparticle (CrNano) on growth, body composition, serum hormones and tissue Cr in Sprague-Dawley (SD) rats. Seventy male SD rats (average initial body weight of (83.2+/-4.4) g) were randomly assigned to seven dietary treatments (n=10). At the end of the trial, body composition was assessed via dual energy X-ray absorptiometry (DEXA). All rats were then sacrificed to collect samples of blood, organs and tissues for determination of serum hormones and tissue Cr contents. The results indicated that lean body mass was significantly increased (P<0.05) due to the addition of 300 and 450 ppb Cr from CrNano. Supplementation of 150, 300, 450, and 600 ppb Cr decreased (P<0.05) percent body fat significantly. Average daily gain was increased (P<0.05) by addition of 75, 150, and 300 ppb Cr and feed efficiency was increased (P<0.05) by supplementation of 75, 300, and 450 ppb Cr. Addition of 300 and 450 ppb Cr decreased (P<0.05) the insulin level in serum greatly. Cr contents in liver and kidney were greatly increased (P<0.05) by the addition of Cr as CrNano in the dosage of from 150 ppb to 1 200 ppb. In addition, Supplementation of 300, 450, and 600 ppb Cr significantly increased (P<0.05) Cr content in the hind leg muscle. These results suggest that supplemental CrNano has beneficial effects on growth performance and body composition, and increases tissue Cr concentration in selected muscles.

Dyslipidemia, often found in type 2 diabetes mellitus (T2DM) patients, plays an important role in the progression of cardiometabolic syndrome. Two essential nutrients, chromium and biotin, may maintain optimal glycemic control. The authors report here a randomized, double-blind placebo-controlled trial (N=348; chromium picolinate and biotin combination [CPB]: 226, placebo: 122; T2DM participants with hemoglobin A1c [HbA1c] >or=7%) evaluating the effects of CPB on lipid and lipoprotein levels. Participants were randomly assigned (2:1 ratio) to receive either CPB (600 microg chromium as chromium picolinate and 2 mg biotin) or a matching placebo once daily for 90 days. Statistical analyses were conducted in all eligible participants. Subsequent supplemental analyses were performed in T2DM participants with hypercholesterolemia (HC) and in those using stable doses of statins. In the primary analysis, CPB lowered HbA1c (P<.05) and glucose (P<.02) significantly compared with the placebo group. No significant changes were observed in other lipid levels. In participants with HC and T2DM, significant changes in total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and atherogenic index were observed in the CPB group (P<.05). Significant decreases in LDL-C, total cholesterol, HbA1c , and very low-density cholesterol levels (P<.05) were observed in the CPB group taking statins. CPB treatment was well tolerated with no adverse effects, dissimilar from those associated with placebo. These data suggest that intervention with CPB improves cardiometabolic risk factors.

Background: The CoStar stent is a novel cobalt chromium stent designed specifically for drug delivery. The COSTAR I trial represents the first-in-man study of the CoStar Paclitaxel-Eluting Coronary Stent System evaluating three dose release formulations of paclitaxel in a bioresorbable polymer matrix in the treatment of de novo coronary lesions., Methods: The COSTAR I Trial was a prospective, multi-center registry enrolling 87 patients in four Indian centers for treatment of up to two de novo lesions = 25 mm in length in a reference vessel 2.5-3.5 mm in diameter. Three dose release formulations were studied: 30 microg eluted over 10 days bidirectionally (Group 1, n =10), 10 microg eluted over 30 days abluminally (Group 2, n=40) and 3 microg eluted over 30 days abluminally (Group 3, n = 37)., Results: Demographics and lesion characteristics were similar between the groups and treatment in all three groups included small caliber vessels (RVD 2.45 +/- 0.30 - 2.57 +/- 0.36 mm). The primary endpoint of in-stent late loss at four months was lowest in Group 2 (0.43 +/- 0.43 mm) compared to Group 1 and Group 3 (0.51 +/- 7 mn; 0.74 mm and 1.07 +/- 0.65 mm respectively). In-segment late loss followed similar trends, being lowest in Group 2 (0.24 +/- 0.39 mm) compared to Groups 1 and 3 (0.52 +/- 0.66 mm and 0.76 +/- 0.57 mm respectively). Group 2 demonstrated better angiographic out-comes at 12 months with in-stent late loss of 0.55 +/- 0.38 mm when compared to Groups 1 and 3 (0.90 +/- 0.76 mm and 0.74 +/- 0.55 mm respectively). Cumulative binary restenosis rates at twelve months were 1.9%, 35.7% and 39.1% in Groups 2, 1 and 3 respectively. Clinical outcomes trended similarly with cumulative MACE rates at twelve months being lowest at 7.5% in Group 2 as compared to 20% in Group 1 and 21.6% in Group 3 respectively., Conclusions: In this first-in-man feasibility trial, angiographic and clinical results seen with the extended release formulation at a higher dose (10 microg/30 days) demonstrate the feasibility of the CoStar stent platform in the treatment of native coronary lesions. It also demonstrates the importance of drug dose and release kinetics.

The first article describes in detail problems connected with the role of macro minerals: Ca, Mg, P, Na, K, Cl in the diet of pregnant and breast feeding women. We concentrated on the choice of good natural sources of micro minerals: Fe, Zn, Cu, Se, I, F, Mn, Mo and Cr. The amounts of the elements in some of the food products are listed and factors that decide on their bioavailability are described. We mentioned pernicious effects of inadequate intake of micro minerals on the health of pregnant women and newborn babies.

In this study, 12 months old female Swiss albino rats were used. They were randomly divided into four groups. The animals of group I were fed with pellet chow. Group II were fed with pellet chow and treated with 250 microg/kg CrCl3 x 6H2O and 100 mg/kg niacin for 45 days. Group III were fed a lipogenic diet consisting of 2% cholesterol, 0.5% cholic acid and 2% sunflower oil added to the pellet chow, and given 3%alcoholic water for 60 days. Group IV were fed with the same lipogenic diet for 60 day sand treated by gavage technique to rats at a dose of 250 micro/kg CrCl3 x 6H2O and 100 mg/kg niacin for 45 days, 15 days after experimental animals were rendered hyperlipidemic. At the 60th day, renal tissue and blood samples were taken from the animals. The sections were examined under light and electron microscopy. The degenerative changes were much more in the hyperlipidemic rats than the control group. The changes in renal tissue were also observed in hyperlipidemic animals given niacin and chromium. In the hyperlipidemic rats, renal glutathione levels decreased and renal lipid peroxidation levels, and serum urea and creatinine levels were increased. But, renal glutathione levels increased and lipid peroxidation levels and serum urea and creatinine levels decreased in hyperlipidemic rats given niacin and chromium. The purpose of this study was to investigate whether a protective effect of a combination of niacin and chromium is present on the renal tissue of hyperlipidemic rats or not. In conclusion, we can say that niacin and chromium do not have a protective effect on the morphology of the renal tissue of hyperlipidemic rats, except a protective effect on their biochemical parameters.

Objectives: The present study was carried out to determine the effect of chromium(VI) on the status of plasma lipid peroxidation and erythrocyte antioxidant enzymes in workers exposed to chromium during chromium plating process., Methods: Fifty subjects working in chromium plating process formed the study group. An equal number of age-sex matched subjects working in administrative units formed the control group. The control subjects were residing in the same city but away from the work place of study group subjects. Urinary chromium levels were determined by using a graphite furnace atomic absorption spectrophotometer. The plasma lipid peroxidation and erythrocyte antioxidant enzymes were determined by using spectrophotmetric methods., Results: A significant increase of plasma lipid peroxidation and a significant decrease of superoxide dismutase and glutathione peroxidase levels were noted in the study group as compared with the controls. The level of plasma lipid peroxidation was positively and erythrocyte antioxidant enzymes were negatively and significantly correlated with chromium levels in urine. Multiple regression analysis was assessed the oxidative stress associated with chromium and life style confounding factors such as BMI, coffee, tea, alcohol and smoking. The multiple regression analysis showed that the urine chromium levels >10 micro g/g of creatinine, smoking, consumption of green vegetables and BMI variables were significantly associated with the levels of oxidative stress., Conclusion: The results show that the increased plasma lipid peroxidation and decreased antioxidant enzymes (superoxide dismutase and glutathione peroxidase) observed in chromium-exposed workers could be used as biomarkers of oxidative stress.

The effects of oral niacin-bound chromium (NBC) supplementation on the subcutaneous fat tissue of type 2 Lepr(db) obese diabetic mice were examined using high-density comprehensive mouse genome (45,101 probe sets) expression arrays. The influence of such supplementation on the plasma cardiovascular risk factors of these mice was also investigated. Supplementation of NBC had no significant effect on age-dependent weight gain in the Lepr(db) obese diabetic mice. However, NBC lowered total cholesterol (TC), TC-to-HDL ratio, LDL cholesterol, and triglyceride levels while increasing HDL cholesterol in the blood plasma. No effect of NBC supplementation was observed on fasting blood glucose levels. Oral glucose tolerance test revealed a significantly improved clearance of blood glucose between 1 and 2 h of glucose challenge in NBC-supplemented mice. Unbiased genome-wide interrogation demonstrated that NBC resulted in the upregulation of muscle-specific gene expression in the fat tissue. Genes encoding proteins involved in glycolysis, muscle contraction, muscle metabolism, and muscle development were specifically upregulated in response to NBC supplementation. Genes in the adipose tissue that were downregulated in response to NBC supplementation included cell death-inducing DNA fragmentation factor (CIDEA) and uncoupling protein-1, which represent key components involved in the thermogenic role of brown adipose tissue and tocopherol transfer protein, the primary carrier of alpha-tocopherol to adipose tissue. The observation that CIDEA-null mice are resistant to obesity and diabetes suggests that the inhibitory role of NBC on CIDEA expression was favorable. Further studies testing the molecular basis of NBC function and long-term outcomes are warranted.

Chromium(VI) compounds are genotoxic in a variety of cellular systems. Their potential carcinogenicity is affected by toxicokinetic patterns restricting bioavailability to certain targets, and by metabolic pathways affecting interaction of chromate-derived reactive species with DNA. Epidemiological data indicate that chromium(VI) can be carcinogenic to the human respiratory tract following inhalation at doses that are only achieved in certain occupational settings. However, concern has been raised that adverse effects may also result from oral intake. In order to further explore this issue, we performed studies in BDF1 and Swiss mice of both genders and various age. Sodium dichromate dihydrate and potassium dichromate were administered either with the drinking water, up to a concentration of 500 mg chromium(VI)/l for up to 210 consecutive days, or in a single intragastric dose of 17.7 mg/kg body weight. Under these conditions, no increase of the micronucleus frequency was observed in either bone marrow or peripheral blood erythrocytes. Conversely, the same compounds induced a clastogenic damage following intraperitoneal injection, which by-passes detoxification mechanisms. In addition, due to the hypothesis that susceptibility may be increased during the period of embryogenesis, we treated pregnant mice, up to a concentration of 10mg chromium(VI)/l drinking water. There was no effect on the numbers of fetuses/dam and on body weight of fetuses. Again, no toxic or genotoxic effect was observed either in bone marrow of pregnant mice or in liver and peripheral blood of their fetuses. Thus, even at doses that largely exceed drinking water standards (up to 10,000 times) or by massive intragastric administration, chromium(VI) is not genotoxic to hematopoietic cells of either adult mice or transplacentally exposed fetuses. These conclusions are consistent with the poor toxicity and lack of carcinogenicity of oral chromium(VI), and are mechanistically explained by the high efficiency of chromium(VI) detoxification processes in the gastrointestinal tract.

Chromium is well documented as an essential element for humans. Trivalent chromium, the main chemical form found in foods, is essential for maintaining normal glucose metabolism. Owing to analytical difficulties, several literature reports of chromium content of foods, especially for the lower levels, show large variability and should be interpreted with caution. Zeeman background correction, transversely heated graphite furnace atomic absorption spectrometry was used to determine the chromium content of 104 different infant formulae (cow's milk and soy protein based) marketed in Spain following an acid-digestion sample preparation procedure in a closed, pressurized and microwave digestion unit. The mean and range of chromium values, regarding types and main protein-based infant formulae are presented. Additionally, the influence of the type of container used, the impact of industrial process from different manufacturers and the physical state (powder and liquid formulae) on chromium levels is also discussed. In general, the infant formulae contain a higher chromium concentration than that found in human milk (reference range: 0.20-8.18 microg l-1), particularly in the case of hypoallergenic (18.16 +/- 7.89 microg l-1), lactose-free (11.37 +/- 3.07 microg l-1), pre-term (11.48 +/- 3.15 microg l-1) and soya (10.43 +/- 4.05 microg l-1) formulae. The maximum theoretical estimated intake of infants fed on the studied formulae was lower than the upper limit safety for trivalent chromium of 1 mg kg-1 (14 microg kg-1 b.w. day-1) recommended by the experts of Council for Responsible Nutrition (Hathcock 2004; available at: http://crnusa.org/safety.html), amounting to about 10, 15-18 and 26% of the standard (adapted and follow-up) and toddler, soya, lactose-free and pre-term, and hypoallergenic formulae, respectively. Therefore, manufacturers are called upon to make continued efforts to routinely monitor chromium levels, particularly for specialised and pre-term formulae, and at the same time, might consider the inclusion of labelling the levels of chromium at least in these complex formulations.

Chromium is generally believed to be an essential element and is often claimed to have value as a weight loss or muscle building agent. Recent studies in humans and rats have failed to demonstrate effects on body composition, although recent studies with pharmacological doses of the cation [Cr(III)3O(O2CCH2CH3)6(H2O)3]+ (or Cr3) (< or =1 mg Cr/kg body mass) in rats have noted a trend toward body mass loss and fat mass loss. Thus, the effects of large gavage doses of Cr3 (1-10 mg Cr/kg) on body mass, organ mass, food intake, and blood plasma variables (insulin, glucose, leptin, cholesterol, and triglycerides) were examined over a 10-wk period using male Sprague-Dawley rats. No effects on body composition were noted, although Cr3 administration lowered (p < 0.05) plasma insulin, leptin, and triglycerides concentrations. As Cr3 is absorbed greater than 10-fold better than commercially available nutritional supplements, the lack of an effect of the Cr(III) compound at these levels of administration clearly indicates that Cr(III) supplements do not have an effect on body composition at any reasonable dosage.

Accurate determination of the flow of nutrients at the omasum requires the use of a triple marker system. Typically, a system based on ruminal administration of the lithium salt of CoEDTA, ytterbium acetate (Yb-Ac), and chromium-mordanted straw (Cr-S) has been used. However, there is evidence to suggest that product:substrate ratios for stearoyl-coenzyme A desaturase (Delta(9)-desaturase) are lower in milk fat from cows administered a combination of CoEDTA, Yb-Ac, and Cr-S, indicating reduced Delta(9)-desaturase activity. To evaluate this hypothesis, samples of milk were collected 1 d before, and on d 2, 6, and 9 of administering the CoEDTA, Yb-Ac, and Cr-S triple marker system into the rumen of 4 cows. A 4 x 4 Latin square with 28-d experimental periods was used to assess the effects of 0, 75, 150, and 300 g/d of fish oil in the diet on ruminal and mammary lipid metabolism. Irrespective of the amount of fish oil in the diet, concentrations of all milk fatty acids containing a cis-9 double bond were reduced after markers were given. Milk fatty acid pairs dependent on Delta(9)-desaturase were decreased over time, with responses reaching a nadir within 6 d of marker administration. Overall, administering markers into the rumen was associated with a mean decrease in milk cis-9 10:1/ 10:0, cis-9 12:1/12:0, cis-9 14:1/14:0, cis-9 16:1/16:0, cis-9 17:1/17:0, cis-9 18:1/18:0, and cis-9,trans-11 conjugated linoleic acid/trans-11 18:1 concentration ratios of 44.6, 52.7, 58.7, 36.8, 37.2, 44.3, and 43.0%, respectively. In conclusion, one or more of the markers administered altered milk fatty acid composition and may act as an inhibitor of Delta(9)-desaturase in the bovine mammary gland.

This study reports a survey of occupational exposure to copper chrome arsenic (CCA) based wood preservatives during vacuum pressure timber impregnation. The survey involved biological monitoring based on analysis of chromium and arsenic in urine samples collected from UK workers. The aim of the study was to determine the extent of occupational exposure to arsenic and chromium in the UK timber treatment industry. The objectives were to collect and analyse urine samples from as many workers as possible, where CCA wood preservatives might be used, at 6 monthly intervals for 2 years. In addition, to investigate day-to-day variations in urinary excretion of chrome and arsenic by collecting and analysing three samples a week for 3 weeks in subsets of workers and controls (people not occupationally exposed). All urine samples were analysed for chromium and inorganic arsenic. To investigate any residual interference every sample was accompanied by a short questionnaire about recent consumption of seafood and smoking. The analytical methods for arsenic used a hydride generation technique to reduce interference from dietary sources of arsenic and also a technique that would measure total arsenic concentration in urine. The main findings show that workers exposed to CCA wood preservatives have concentrations of inorganic arsenic and chromium in urine that are significantly higher than those from non-occupationally exposed people but below biological monitoring guidance values that would indicate inhalation exposure at UK occupational exposure limits for chromium and arsenic. The effects of consumption of seafood on urinary arsenic were not significant using the hydride generation method for inorganic arsenic but were significant if 'total' arsenic was measured. The 'total' arsenic method could not distinguish CCA workers from controls and is clearly unsuitable for assessment of occupational exposure to arsenic. There was a significant increase in the urinary concentration of chromium in workers over the four sample collection rounds indicating increasing exposure to chromium during the 2 years of the study. This unexpected finding may be worth further investigation. Overall, the study demonstrated the utility of biological monitoring for assessment of occupational exposure to chromium and arsenic.

More than half of the U.S. population has a body mass index of 25 kg/m2 or more, which classifies them as overweight or obese. Obesity is often associated with comorbidities such as diabetes, cardiovascular diseases, and cancer. CLA and chromium have emerged as major dietary supplements that reduce body weight and fat mass, and increase basal metabolic rate in animal models. However, studies show that CLA induces insulin resistance in mice and in humans, whereas Cr improves insulin sensitivity. Hence, we designed the present study to examine the combined effect of CLA and Cr on body composition and insulin sensitivity in a Balb/c mice (n = 10/group) model of high-fat-diet-induced obesity. CLA alone lowered body weight, total body fat mass, and visceral fat mass, the last of which decreased further with the combination of CLA and Cr. This effect was accompanied by decreased serum leptin levels in CLA-fed and CLA + Cr-fed mice, and by higher energy expenditure (EE) and oxygen consumption (OC) in CLA + Cr-fed mice. Serum levels of glucose, insulin, the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), as well as insulin resistance index (IRI), decreased with CLA, whereas CLA and Cr in combination had significant effects on insulin and IL-6 concentrations and IRI. In summary, CLA + Cr decreased body weight and fat mass in high-fat-diet-fed mice, which may be associated with decreased leptin levels and higher EE and OC.

The aim of this study was to determine the effect of chromium (Cr)- enriched yeast on blood glucose and insulin variables, blood lipids, and blood markers of oxidative stress in persons with type 2 diabetes mellitus (median duration: 3.0 yr). Thirty-six subjects (9 men, 27 women; mean age: 61.3 yr; mean body mass index: 34.33 kg/m2) were supplemented with 400 microg Cr/d as Cr-enriched yeast (n = 19) or placebo (n = 17) for 12 wk in a randomized, double-blind study. The most interesting results were obtained by comparison of the change in the placebo group to the change in the Cr group. The Cr group showed a significantly greater increase in serum Cr compared to the placebo group (p < 0.05). Supplementation with Cr-enriched yeast was associated with a significant decrease in fasting serum glucose compared to placebo (p < 0.01). Blood markers of oxidative stress glutathione peroxidase activity and levels of reduced glutathione were essentially unchanged in the Cr group after 12 wk, but decreased significantly in the placebo group (p < 0.05, p < 0.01, respectively). Serum HbA1c and glycated protein (fructosamine) were essentially unchanged in the Cr group, whereas HbA1c tended to increase in the placebo group (from 6.94% to 7.11%). Fasting serum insulin decreased in both groups, with a greater tendency in the Cr group (-16.5% vs -9.5%). These data suggest that supplementation of well-controlled type 2 diabetics with Cr-enriched yeast is safe and can result in improvements in blood glucose variables and oxidative stress.

Background: Chromium plays a role in insulin sensitivity., Objectives: To compare chromium measurements in HIV-positive patients with or without (N) antiretroviral therapy (ART) to that of healthy controls (HC) and, to determine if there is any association between chromium levels and abnormalities in body composition, glucose and lipid metabolism., Design: A cross-sectional study in 91 HIV patients (75 HIV-ART, 16 HIV-N) and 13 HC. Chromium was assessed in the diet, plasma, toenails, and urine. Fasting blood glycemia and lipids, lipodystrophy score and body fat were also determined., Results: Dietary intake of chromium was similar in the 3 groups. Plasma and toenail Cr were lower in HIV compared to HC, but urinary chromium was similar. However, when the HIV-positive patients on ART were compared to those who were naïve to therapies, urinary excretion of chromium was higher in HIV-ART. In addition, urinary excretion of chromium significantly and positively correlated with lipodystrophy score and negatively with various parameters of metabolic syndrome., Conclusion: Despite a similar dietary intake, chromium levels were lower in HIV-positive patients and urinary chromium excretion correlated with some metabolic parameters. Low chromium levels may be due to increased chromium losses. These results support further studies on chromium in HIV patients.

The exposure-response relationship for airborne hexavalent chromium exposure and lung cancer mortality is well described by a linear relative rate model. However, categorical analyses have been interpreted to suggest the presence of a threshold. This study investigates nonlinear features of the exposure response in a cohort of 2,357 chemical workers with 122 lung cancer deaths. In Poisson regression, a simple model representing a two-step carcinogenesis process was evaluated. In a one-stage context, fractional polynomials were investigated. Cumulative exposure dose metrics were examined corresponding to cumulative exposure thresholds, exposure intensity (concentration) thresholds, dose-rate effects, and declining burden of accumulated effect on future risk. A simple two-stage model of carcinogenesis provided no improvement in fit. The best-fitting one-stage models used simple cumulative exposure with no threshold for exposure intensity and had sufficient power to rule out thresholds as large as 30 microg/m3 CrO3 (16 microg/m3 as Cr+6) (one-sided 95% confidence limit, likelihood ratio test). Slightly better-fitting models were observed with cumulative exposure thresholds of 0.03 and 0.5 mg-yr/m3 (as CrO3) with and without an exposure-race interaction term, respectively. With the best model, cumulative exposure thresholds as large as 0.4 mg-yr/m3 CrO3 were excluded (two-sided upper 95% confidence limit, likelihood ratio test). A small departure from dose-rate linearity was observed, corresponding to (intensity)0.8 but was not statistically significant. Models in which risk-inducing damage burdens declined over time, based on half-lives ranging from 0.1 to 40 years, fit less well than assuming a constant burden. A half-life of 8 years or less was excluded (one-sided 95% confidence limit). Examination of nonlinear features of the hexavalent chromium-lung cancer exposure response in a population used in a recent risk assessment supports using the traditional (lagged) cumulative exposure paradigm: no intensity (concentration) threshold, linearity in intensity, and constant increment in risk following exposure.

Increased intracellular free calcium [Ca2+]i has been noted in adipocytes, platelets, and leukocytes of subjects with insulin resistance syndrome or allied disorders. In rodent studies, measures which increase [Ca2+]i in adipocytes and skeletal muscle are associated with impaired insulin signaling, attributable at least in part to diminished ability of insulin to activate phosphoserine phosphatase-1 (PP-1). In fat-fed insulin resistant rats, pre-treatment with a drug that selectively chelates intracellular calcium eliminates about half of the decrement in insulin-stimulated glucose uptake induced by fat feeding; since this chelator does not influence the insulin sensitivity of chow-fed rats, it is reasonable to suspect that fat feeding boosts [Ca2+]i in skeletal muscle, and that this effect is partially responsible for the associated reduction in insulin sensitivity. Clinical insulin resistance is associated with increased levels of triglycerides and other fatty acid metabolites in muscle fibers; this can give rise to diacylglycerol-mediated activation of PKC, which in turn compromises insulin signaling by triggering kinase cascades that phosphorylate IRS-1 on key serine residues. Yet there is also evidence that, in skeletal muscle, PKC activity up-regulates the function of L-type calcium channels, increasing their maximal conductance while left-shifting their voltage dependence. Thus, the PKC activation associated with fat overexposure might be expected to boost basal [Ca2+]i in skeletal muscle, potentially impeding insulin-mediated activation of PP-1. This hypothesis is consistent with several clinical studies demonstrating that long-acting inhibitors of L-type calcium channels can improve insulin sensitivity in overweight hypertensives; it should be readily testable in rodent models of fat-induced insulin resistance. Since parathyroid hormone can act on adipocytes and muscle to boost [Ca2+]i, mild secondary hyperparathyroidism associated with low calcium intakes and poor vitamin D status may contribute to insulin resistance, consistent with certain clinical and epidemiological findings. Magnesium, often thought of as a mild calcium antagonist, appears to have favorable effects on insulin sensitivity and risk for diabetes, and recent evidence indicates that increases of intracellular magnesium within the physiological range can diminish calcium influx through phosphorylated L-type calcium channels. It will be of interest to determine whether calcium antagonism does indeed underlie the favorable influence of good magnesium status on insulin function. A report that chromium picolinate can induce the plasmalemmal Ca2+-ATPase in smooth muscle cells, raises the possibility that modulation of calcium transport might play a role in the insulin-sensitizing efficacy of bioactive chromium.

Since the species that trigger chromium allergy are not yet known, it is important to gain more of an insight into the mechanism of chromium transport through the skin and into the relationship between chromium allergy and chromium species. In vitro permeation studies with porcine and human skin were performed using a Franz static diffusion cell. Investigations attempted to elucidate (i) which Cr compounds are able to permeate through skin, (ii) the influence the Cr concentration in the donor solution has on the Cr permeation, and (iii) the effect that the time of exposure to the donor solution has on Cr permeation. Capillary electrophoresis hyphenated to inductively coupled plasma-sector field mass spectrometry (CE-ICP-SFMS) was used to separate and quantify the Cr species in the receptor fluid. 50 mmol L(-1) phosphate buffer (pH 2.5) was used for CE separation, and two different electrophoretic runs were carried out (in the positive and negative modes). Pneumatic nebulization (PN)-ICP-SFMS was used in order to quantify the total amount of Cr absorbed by the skin after microwave-assisted acid digestion of the tissue. Cr(VI) was found to pass most easily through the skin. Nevertheless, Cr(VI) was also shown to be absorbed more efficiently by the skin than Cr(III), an observation attributed to a more pronounced rejection of the positively charged Cr(III) ions by the skin barrier. These results were in good agreement with in vitro permeation studies previously reported in the literature in which other analytical techniques were used. Differences observed in the permeation of Cr following the application of aqueous Cr donor solutions and Cr-containing simulated sweat donor solutions are also described.

Chromium is an essential trace element required for normal protein, fat and carbohydrate metabolism. It also helps in energy production and increasing lean body mass. Niacin-bound chromium (NBC) is a unique form of bioavailable chromium that promotes healthy lipid profile. This study was focused on determining the broad spectrum safety of NBC. Acute oral, acute dermal, primary dermal irritation and primary eye irritation toxicities of NBC were evaluated. Ames bacterial reverse mutation assay, mouse lymphoma test and a dose-dependent 90-day subchronic toxicity were also conducted. In safety studies, the acute oral LD(50) of NBC was found to be greater then 5000 mg/kg in both male and female Sprague-Dawley rats. No changes in body weight or adverse effects were observed following necropsy. The acute dermal LD(50) of NBC was found to be >2000 mg/kg. The primary skin irritation test was conducted with NBC on New Zealand Albino rabbits. NBC was classified as slightly irritating. The primary eye irritation test was conducted with NBC on rabbits. NBC was classified as practically non-irritating to the eye. NBC did not induce mutagenic effects in the bacterial reverse mutation test in five Salmonella typhimurium strains (TA1535, TA98, TA100, TA97a and TA102), either with or without metabolic activation. Similarly, NBC did not induce mutagenic effects in the mammalian cell gene mutation test in L5178Y mouse lymphoma cells TK (+/-), either with or without metabolic activation. A dose-dependent 90-day subchronic toxicity study demonstrated no significant changes in selected organ weights individually and as percentages of body and brain weights. NBC supplementation did not cause changes in hepatic lipid peroxidation or DNA fragmentation after 30, 60 or 90 days of treatment. Hematology, clinical chemistry and histopathological evaluations did not show any adverse effects in all organs tested. Taken together, the above results indicate a broad spectrum of safety for NBC.

Background & Objective: The occupational and non-occupational exposure to hexavalent chromium Cr (VI) is common. The effect of chromium compromises the immune response of the host. Dengue virus (DV) infection causes various changes in the peripheral blood cells. It is, therefore, possible that the chromium toxicity may affect the disease process during DV infection. The present study aims to study the effects of dengue virus infection on peripheral blood cells of mice fed Cr (VI) with drinking water., Methods: One group of mice was given ad libitum drinking water containing Cr (VI) and the other group used as the normal control mice was given plain water to drink. At the 3, 6 and 9 wk of Cr (VI) drinking, a set of mice from each group was inoculated intracerebrally (ic) with DV and studied at the 4th and 8th day post inoculation., Results: It was observed that Cr (VI) drinking led to reduction in lymphocytes, haemoglobin and the haematocrit values while the granulocyte, monocyte and platelet counts were increased. On the other hand, most of the parameters were decreased following inoculation of normal mice with DV. In Cr (VI)-fed mice the effects of DV infection were minimal. The most significant finding of these experiments was that the reduction in platelet counts following inoculation with DV was markedly less in Cr (VI)-fed mice than that in DV-inoculated normal control mice., Interpretation & Conclusion: Cr(VI) compounds have been declared as a potent occupational carcinogen. On the contrary, Cr(III) salts such as chromium polynicotinate, chromium chloride and chromium picolinate, are used as micronutrients and nutritional supplements, and have been shown to exhibit health benefits in animals and humans. Whether therapeutic doses of chromium (III) compounds may be able to prevent the DV-induced fall in platelet counts, needs to be investigated.

The potential toxicity of metal ions in tissues surrounding metal-metal hip replacements is a cause for concern. Previous studies conducted in our laboratory demonstrated that Co(2+) and Cr(3+) induce TNF-alpha secretion in macrophages, as well as cell mortality. However, the degree of apoptosis and necrosis remained to be investigated. The aim of the present study was to quantify the rate of macrophage mortality by apoptosis vs. necrosis induced by Co(2+) and Cr(3+). J774 mouse macrophages were incubated in growth medium containing 0-10 ppm Co(2+) and 0-500 ppm Cr(3+) for 24 and 48 h under conventional cell culture conditions. Transmission electron microscopy, flow cytometry (Annexin-V fluorescein isothiocyanate/propidium iodide assay) and a specific cell death detection ELISA were used to illustrate cell death and differentiate between apoptotic and necrotic cells. Cell culture exposed to low concentrations of Co(2+) (0-6 ppm) revealed a low degree of mortality. In contrast, at the highest concentrations (8-10 ppm), late apoptosis occurred within 24 h. After 48 h, however, there was a clear evidence for an increase in the rate of necrosis while apoptosis occurred at much lower rate. Macrophages exposed to Cr(3+) demonstrated a predominance of apoptosis after 24h. At concentrations lower than 250 ppm, early and late apoptosis occurred at the same rate. At higher concentrations (250-500 ppm), the number of early apoptotic cells decreased in favor of late apoptosis. After 48 h, lower concentrations of Cr(3+) (150 ppm) induced a higher degree of early apoptosis than after 24 h, and some necrosis. At higher concentrations, the percentage of early apoptotic cells decreased, while necrosis became predominant over late apoptosis. In conclusion, this study demonstrates that macrophage mortality induced by metal ions depends on the type and concentration of metal ions as well as the duration of their exposure. Overall, apoptosis was predominant after 24 h with both Co(2+) and Cr(3+) ions, but high concentrations induced mainly necrosis at 48 h. These results point to the potential for these ions of inducing tissue damage by necrosis if present in large concentrations in vivo.

Objective: To study the regulation of chromium on gene expression related to metabolism of skeletal muscles in diabetic rats., Methods: Male Wistar rats were assigned to three groups: normal control group (NC), alloxan-induced diabetic control group (DM), and DM with chromium supplementation group (DM + Cr). 200 microg Cr/kg bw perday was supplemented orally for 60 days. At the end of the treatment, the changes in gene expression among three groups were studied by mRNA differential display technique combined with cDNA fragments cloning, sequencing and BLASTn analysis., Results: 11 cDNA fragments larger than 400bp expressed differences in skeletal muscles between DM + Cr group and DM group were isolated, 4 of them expressed higher in DM + Cr group, while the rest expressed higher in DM group. Cr-3 and GLUT4 are homologous with sequence identities of 98% and Cr-5 and IRS-1 are homologous with sequence identities of 100%. The expression level of GLUT4 mRNA in DM + Cr group are higher than those of DM group., Conclusion: Chromium supplementation could induce the expression of GLUT4 mRNA on skeletal muscles in diabetic rats. It may be one of the molecular mechanisms that chromium could improve the disorders of glucose and lipids metabolism in diabetic rats.