Chromium Excretion Research Articles

Long-Term Clinical and Toxicological Follow-up of Severe Cobalt and Chromium Intoxication—a Case Report

Cobalt intoxications from fractured hip endoprostheses have been described since the early 2000s. Typical symptoms include cardiomyopathy, neurological symptoms with visual and hearing loss and hypothyroidism. Less is known about long-term progression of these pathologies. This case report shows the long-term course of complications caused by cobalt and chromium exposure after substantial elimination of the source of intoxication. We report here a 63-year-old male Caucasian with severe cobalt and chromium intoxication. He presented 1 month after 2nd revision surgery of a broken hip endoprosthesis in a reduced general condition with signs of heart failure, pale skin and diminished hearing and vision. Blood analyses showed a cobalt concentration of 600 μg/L (reference value < 0.45 μg/L). Because the blood cobalt concentration decreased rapidly after surgery and symptoms improved, chelation therapy was not applied. Close clinical and toxicological monitoring was performed. The intoxication was not diagnosed until 6 years after the faulty hip joint revision and 3 years of clear signs of intoxication during a 2nd revision of the prosthesis. The patient’s ordeal could have been much shorter if his cobalt intoxication with neurologic, cardiac and thyroid symptoms had been detected earlier by toxicological blood tests. After the elimination of the source of poisoning, the long-term course showed constant excretion of cobalt and chromium over several years without chelation. Specific symptoms such as cardiomyopathy and neurological symptoms were declining. However, due to the continuous release of metal ions from the tissue, complete recovery did not occur.

RELATIONSHIP BETWEEN S-INSULIN AND CHROMIUM, MANGANESE, COBALT, AND ZINC EXCRETION IN THE URINE IN HEALTHY KHYBER PAKHTUNKHWA PERSONS

Objective: Clinical research has shown that mineral imbalances, including those involving zinc, cobalt, manganese,and chromium, are crucial for the onset and development of diabetes mellitus. To ascertain the function of these traceelements in pathogenesis and the advancement of type 2 diabetes, this investigation aimed to ascertain if there was alink, if any, between the urine excretion of these minerals and s-insulin levels.Study Design: Cross-sectional study.Place and Duration of study: From January to December 2013, this research was carried out at Khyber MedicalUniversity (KMU), Peshawar, at the Institute of Basic Medical Sciences (IBMS).Materials and Methods: This research comprised 200 healthy people from the seven divisions of Khyber Pakhtunkhwa (Abbottabad, Peshawar, Mardan, Bannu, Dera Ismail Khan, Malakand, and Kohat) with normal fastingblood sugar (FBS), creatinine, cholesterol, HDL, LDL, and TAG values. Anthropometric measures and demographicdata were recorded. Serum creatinine, serum insulin, lipid profile, and fasting blood sugar were measured using a bloodsample. Urine samples were taken early in the morning to measure zinc, cobalt, manganese, and chromium levels.Results: It was discovered that there was a near-to-significant negative connection (r: -0.127, p: 0.073) betweenmanganese and s-insulin and a considerably high negative correlation (r: -0.191, p: 0.007) between chromium ands-insulin. Thus, elevated chromium and manganese excretion in the urine in healthy persons may eventually causeT2DM to proceed if improperly managed.Conclusion: the present study revealed a significant correlation of s-insulin with urinary excretion of chromium only.Keywords: Type II diabetes mellitus, s-insulin, trace elements.

Influence of organic chromium supplementation on the performance of beef calves undergoing weaning-related stress

ABSTRACT: Dietary chromium supplementation before, during, and after weaning was conducted to evaluate the hypothesis that chromium supplementation could reduce weaning-induced cortisol release in beef calves. We examined the effects of chromium supplementation in 150 crossbred calves (male and female) between five and six months of age. The calves were randomly divided by sex and breed into two equal homogeneous groups (n=75). One group was used as the control, and the other experimental group received supplementation with 0.9mg of chromium carbon-amino-phospho-chelate per 100kg BW. The chromium supplement was mixed with mineral salt for the consumption of 0.1% of BW, and the supplement was administered via creep feeding 60 days before and 60 days after forced weaning. Calves were weighed, and their blood and urine samples were obtained at four time-points: T0 (60 days before weaning), T1 (at weaning), T2 (48 hours after weaning), and T3 (60 days after weaning). Blood samples were used to determine chromium, cortisol, total protein, and albumin concentrations, and urine samples were used to determine urinary creatinine and chromium levels. Cumulative weight gain was higher in calves supplemented with chromium before weaning and during the experiment (P&lt;0.05). In addition, weaning-related stress caused an increase in chromium excretion in the urine, and chromium supplementation reduced stress, which resulted in lower cortisol and total protein levels during weaning.

Grain source and chromium supplementation: Effects on health, metabolic status, and glucose-insulin kinetics in Holstein heifer calves

Carbohydrate-rich diets may increase urinary excretion of chromium (Cr) and the need to supplement the diet with Cr to meet animal requirements. The present study was performed to examine the effect of the type of grain (corn vs. barley) and Cr-methionine supplementation on health-related variables, blood levels of metabolites and hormones related to energy metabolism, and insulin sensitivity in Holstein calves. Forty-eight newborn heifers (3 d of age) were assigned randomly to 4 diets in a 2 × 2 factorial arrangement. Experimental diets were either corn-based (CBD) or barley-based (BBD) diets supplemented with 0 or 0.05 mg/kg of metabolic body weight. Chromium was provided in milk before weaning (d 3-73 of age) and in prewarmed water after weaning (d 74-94 of age). There was no interaction between the type of grain and Cr on the health-related variables and blood metabolites and hormones. Type of grain did not affect fecal score, respiration rate, and rectal temperature; however, there were tendencies for higher diarrhea occurrence (odds ratio = 1.69) and lower chance of having pneumonia (odds ratio = 0.49) in calves fed BBD versus CBD despite longer duration of diarrhea (0.54 d) and shorter days with pneumonia (0.63 d) in calves fed BBD. Calves supplemented with Cr had lower fecal score during the preweaning and overall periods and respiration rate throughout the study. Supplemental Cr decreased the duration (0.63 d) and chance of having pneumonia (odds ratio = 2.01). Calves fed BBD had lower blood levels of urea N during the postweaning period, with no changes in other blood variables between CBD and BBD. Tendencies were detected for lower blood levels of β-hydroxybutyric acid during the preweaning and overall periods and higher cortisol in Cr-supplemented calves. Chromium supplementation increased insulin clearance rate and decreased the time to half-maximal concentration and the area under the curve in BBD but not CBD calves. The calves were generally healthy, and the type of grain did not affect the health and blood variables related to energy metabolism. However, Cr supplementation increased fecal consistency, decreased respiration rate and days with pneumonia, and increased insulin sensitivity when added to BBD.

Effects of work schedule and period of exposure on changes in urinary chromium and nickel excretion among rotating shift workers in a stainless-steel plant

ABSTRACTWe investigated the association between the period of exposure and changes in urinary excretion of chromium and nickel among rotating shift workers in a stainless-steel plant. The study participants were composed of two groups: the workers who were occupationally exposed to metals (“exposed group”) and those who were not occupationally exposed to metals (“unexposed group”). The exposed and unexposed groups consisted of 56 and 40 male rotating shift workers, respectively. Urine samples were collected immediately before and immediately after the day shift, evening shift, and night shift. Urinary chromium and nickel were measured using inductively coupled plasma mass spectrometry. To correct for variations in urine dilution, urinary metal concentrations were expressed as a ratio to urinary creatinine concentration. In the exposed group, post-shift urinary excretion of chromium was significantly higher than pre-shift excretion. However, although urinary chromium excretion clearly increased after the day and night shift [63% (p < .0001) and 87% (p < .0001), respectively], urinary chromium excretion after the evening shift was only slightly higher than that measured before the evening shift (8%, p = .028). Similar patterns were found for urinary nickel excretion (p = .0001, 0.20, and 0.18 for the day, evening, and night shifts, respectively). Non-uniform urinary excretion of metals between the day shift, evening shift, and night shift were observed in the exposed group; specifically, urinary metal excretion increased only slightly during the evening shift. In the unexposed group, no significant increase or decrease was found in median urinary chromium or nickel excretion (p= .63–0.87). Work shift-specific permissible exposure level would be necessary.

Intra-erythrocyte chromium as an indicator of exposure to hexavalent chromium: An in vivo evaluation in intravenous administered rat

Hexavalent chromium (Cr(VI)) compounds are classified as carcinogenic to humans. Whereas chromium measurements in urine and plasma attest to the last few hours of total chromium exposure (all oxidation states of chromium), chromium in red blood cells (RBC) is attributable specifically to Cr(VI) exposure over the last few days.Before recommending Cr in RBC (CrIE) as a biological indicator of Cr(VI) exposure, in vivo studies must be undertaken to assess its reliability. The present study examines the kinetics of Cr(VI) in rat after a single intravenous dose of ammonium dichromate. Chromium levels were measured in plasma, red blood cells and urine. The decay of the chromium concentration in plasma is one-phase-like (with half-life time of 0.55 day) but still measurable two days post injection. The excretion of urinary chromium peaks between five and six hours after injection and shows large variations. Intra-erythrocyte chromium (CrIE) was very constant up to a minimum of 2 days and half-life time was estimated to 13.3 days. Finally, Cr(III) does not interfere with Cr(VI) incorporation in RBC.On the basis of our results, we conclude that, unlike urinary chromium, chromium levels in RBC are indicative of the amount of dichromate (Cr(VI)) in blood.

Grain source and chromium supplementation: effects on feed intake, meal and rumination patterns, and growth performance in Holstein dairy calves

Carbohydrate-rich diets may increase urinary excretion of chromium (Cr) and increase its requirements. This study was conducted to investigate the effect of grain type (barley v. corn) and Cr supplementation on feed intake, feeding behavior and weight gain in dairy calves. Forty-eight neonatal Holstein female calves were assigned randomly to four experimental diets in a 2×2 factorial arrangement. Experimental diets were either barley-based diet (BBD) or corn-based diet (CBD) supplemented with (+Cr) or without (−Cr) Cr as Cr-methionine (0.05 mg/kg of BW0.75). Chromium was provided in milk (from days 3 to 73 of life) during the pre-weaning period and then in pre-warmed water (from day 74 until day 94 of life) after weaning. Meal length tended to increase in calves fed the BBD v. CBD during the pre-weaning period. During the post-weaning period, meal size, inter-meal interval, and eating rate increased concurrently but meal frequency and eating time decreased in the BBD v. CBD. During the pre-weaning period, feed efficiency, BW at weaning, and heart girth increased and non-nutritive oral behaviors tended to decrease with Cr supplementation. Due to increased meal frequency, the starter feed intake but not eating time increased by Cr supplementation during the post-weaning period. Supplementing Cr increased starter feed intake, final BW, average daily gain and heart girth during the overall period. Rumination time increased in BBD+Cr calves due to increases in the frequency and duration of rumination, or decreased rumination bout interval. Overall, the type of grain had no effect on feed intake and growth performance; however, Cr supplementation decreased non-nutritive oral behaviors and increased starter feed intake via increasing the meal frequency and thereby improved growth performance.

Trivalent chromium (CrIII) as a trace element essential for animals and humans

Trivalent chromium is considered an essential element in the nutrition of both animals and humans. Animal studies confirm many beneficial effects of organic and inorganic chromium compounds on carbohydrate, protein and lipid metabolism in the body. Glucose tolerance factor (GTF) has been demonstrated to involve an active form of trivalent chromium, which sustains normal glucose metabolism. Cr(III) compounds form enzymes and ribonucleic acids, accelerate blood clotting and increase β-glucuronidase activity. Chromium also participates in antioxidant processes, in the synthesis of RNA and DNA and in the immune response, as well as affects secretion of hormones and some vitamins. It has been demonstrated that chromium improves lean body mass in animals, increases growth rate and feed conversion and improves feed intake and energy efficiency. Organic chromium reduces mortality and improves animal reproduction parameters. It also enhances immunity and strengthens response to preventive vaccination. It has been noted in many animal species that a diet low in chromium leads to deficiency symptoms, such as reduced feed intake, lower weight gains, reproductive disorders and increased lipid levels. Chromium deficiency can also result from stress. Moderate chromium deficiency is a risk factor of ischemic heart disease with myocardial infarction. Such a condition may pose a great risk of coronary artery disease. Dietary chromium requirement of an animal body is probably 300 μg Cr/kg d.w. of feed, which is usually satisfied by the ration provided. The highest concentration of chromium is found in the hair, skin and teeth, followed by the liver, kidneys, spleen, and slightly lower in the heart, muscles, pancreas, lungs, bones and brain. Chromium absorption rates in the human intestine range between 0.5 and 2% of the daily intake of inorganic Cr forms, and from 25 to 30% of the element ingested as organic complexes. Clinical studies show that the kinetics of chromium excretion from the system are complex and can be described by a multi-range model, the half-life ranging from 13 min to 192 days. Dietary chromium nanocomposite supplementation (CrNano) used in pigs nutrition has significantly increased Cr content in the blood, longissimus muscle, heart, liver, kidneys, jejunum and ileum. Chromium nanocomposite supplementation acts more effectively on the tissues and, as a consequence, increases the accumulation of the element. .

Metabolism, Intake, and Digestibility of Lambs Supplemented with Organic Chromium

The aim of the present study was to evaluate the metabolism of organic chromium and its effect on digestibility and intake of lambs. Four 4-month-old male lambs, each weighing 28 kg, were used. The animals were kept in metabolic cages for a period of 20 days (15 days of adaptation and 5 days of experimentation), in two experimental phases, with inverted treatments. Organic chromium was administered by intraruminal infusion of 1 mg of chromium-rich yeast (Saccharomyces cerevisiae) throughout the adaptive and experimental period. The dry material rates of the diet and feces of the animals were evaluated to estimate consumption, digestibility, and fecal production. During the experimental period, blood, feces, and urine were collected every 24 h to determine chromium levels. There was no significant difference in the excretion of chromium in the urine, and no mineral remnants were detected in the blood. Excretion was generally fecal. There was greater excretion of chromium in the feces of lambs in the treated group on day 0 and day 3, compared with the control group. The use of organic chromium promoted an increase in the consumption of dry material in the treated animals only at day 0 (P <0.05). The production of fecal dry matter was greater among the treated lambs than among the animals of the control group on day 1, day 2, day 3, and day 4 (P <0.05). The results obtained showed that organic chromium associated with live yeasts is not absorbed by the body and do not affect the intake time in the dose used.

Metal-on-Metal Hip Prostheses and Systemic Health: A Cross-Sectional Association Study 8 Years after Implantation

There is public concern over the long term systemic health effects of metal released from hip replacement prostheses that use large-diameter metal-on-metal bearings. However, to date there has been no systematic study to determine which organs may be at risk, or the magnitude of any effect. We undertook a detailed cross-sectional health screen at a mean of 8 years after surgery in 35 asymptomatic patients who had previously received a metal-on-metal hip resurfacing (MoMHR) versus 35 individually age and sex matched asymptomatic patients who had received a conventional hip replacement. Total body bone mineral density was 5% higher (mean difference 0.05 g/cm2, P = 0.02) and bone turnover was 14% lower (TRAP 5b, mean difference −0.56IU/L, P = 0.006; osteocalcin, mean difference −3.08 ng/mL, P = 0.03) in the hip resurfacing versus conventional hip replacement group. Cardiac ejection fraction was 7% lower (mean absolute difference −5%, P = 0.04) and left ventricular end-diastolic diameter was 6% larger (mean difference 2.7 mm, P = 0.007) in the hip resurfacing group versus those patients who received a conventional hip replacement. The urinary fractional excretion of metal was low (cobalt 5%, chromium 1.5%) in patients with MoMHR, but creatinine clearance was normal. Diuretic prescription was associated with a 40% increase in the fractional excretion of chromium (mean difference 0.5%, P = 0.03). There was no evidence of difference in neuropsychological, renal tubular, hepatic or endocrine function between groups (P>0.05). Our findings of differences in bone and cardiac function between patient groups suggest that chronic exposure to low elevated metal concentrations in patients with well-functioning MoMHR prostheses may have systemic effects. Long-term epidemiological studies in patients with well-functioning metal on metal hip prostheses should include musculoskeletal and cardiac endpoints to quantitate the risk of clinical disease.

Urinary Chromium Excretion in Response to an Insulin Challenge Is Not a Biomarker for Chromium Status

Over 50 years ago, chromium (Cr) was proposed to be an essential trace element; however, recent studies indicate that this status should be removed as the effects of Cr supplementation appear to be pharmacological rather than nutritional. The pharmacological basis for Cr's effects can explain the inability of investigators to discover a biomarker for Cr status. One potential biomarker has not been examined to date. Cr is known to be mobilized in the body in response to insulin (or insulin release in response to a glucose challenge), resulting in an increase in urinary Cr excretion. The magnitude of increase in urinary Cr loss as a function of dietary Cr intake was tested as a potential biomarker for Cr. Zucker lean rats housed in carefully controlled metal-free conditions were provided a series of purified diets containing variable Cr contents (from 16 μg/kg diet to 2,000 μg/kg) for 23 weeks. The 16 μg/kg diet contained less Cr than any diet examined to date. Urine samples were collected before and after insulin and glucose challenges (0, 2, 6, and 12 h postinjection). Urinary Cr levels were analyzed by the standard method of addition using graphite furnace atomic absorption. The rate of urinary Cr loss after a glucose or insulin challenge was found to not be dependent on the Cr content of the rats' diets. Blood iron levels of the rats were also measured to determine if the addition of Cr to the diet altered iron status. The Cr content of the diet was found to have no affect on blood iron levels. Overall, the study demonstrated that insulin-stimulated urinary Cr excretion cannot be used as a biomarker for Cr status.

An outbreak of occupational asthma due to chromium and cobalt

Five metal turners employed by an aerospace manufacturer presented to the Birmingham Chest Clinic occupational lung disease unit. Four cases of occupational asthma (OA) due to chromium salt (3) and cobalt (1) were diagnosed by serial peak-expiratory flow measurements and specific inhalation challenge testing. To measure the extent of the outbreak and to provide epidemiological data to ascertain the aetiology. Participants answered a detailed, self-administered questionnaire, designed to detect occupational lung disease. Urine chromium and cobalt excretion, spirometry and exhaled nitric oxide measurements were taken. Those with possible, probable or definite non-OA or OA, after questionnaire, were invited to undertake two-hourly peak flow measurements and received specialist follow-up. A total of 62 workers (95% of workforce) participated. Sixty-one per cent of employees were working in higher metalworking fluid (MWF) exposure areas. Ninety per cent of workers had urinary chromium excretion indicating occupational exposure. Sixty-six per cent of workers reported active respiratory symptoms, although there were no significant differences between exposure groups. Two further workers with probable OA were identified and had significantly higher urinary chromium and cobalt concentration than asymptomatic controls. Eighteen cases of occupational rhinitis (OR) were identified, with significantly raised urinary chromium concentration compared with asymptomatic controls. Chromium salt and cobalt can be responsible for OA and OR in workers exposed to MWF aerosols. Onset of symptoms in those with positive specific challenges followed change in MWF brand. Workers with OA had increased urinary concentrations of chromium and cobalt, and those with OR had increased urinary concentrations of chromium.

Toxic effects of chromium on tannery workers at Sialkot (Pakistan)

Chromium is widely used in the leather industry, and tannery workers are under constant threat of adverse health effects due to its excessive exposure. Our objective was to find out the toxic effects of chromium on tannery workers at Sialkot, Pakistan. A total of 240 males consisting of 120 workers from tanneries at Sialkot and equal number of controls were included. Blood complete counts, high-sensitive C-reactive protein, malondialdehyde and routine biochemical tests were carried out by routine procedures. Chromium levels in blood (BCr) and urine were analyzed using graphite furnace atomic absorption spectrophotometer Perkin Elmer analyst-200. Results revealed that all the workers were male with average age of 33 years and 15 (13%) had skin rashes, 14 (12%) had chronic bronchitis, 10 (8%) had gastritis and 4 (3%) conjunctivitis. The tannery workers had significantly raised median (interquartile range) of BCr 569 (377-726) nmol/L as compared to 318 (245-397) nmol/L in the control (p < 0.001). Sixty-five (54%) workers had BCr levels above the upper limit set by Agency for Toxic Substance and Drug Registry. The urinary chromium excretion was significantly high in workers 131 (46-312) nmol/L as compared to 13 (3-26) nmol/L in controls (p < 0.01). The workers had hematological, hepatic and renal function impairment because of oxidative stress on body systems. It is concluded that about half of the workers had excessive exposure to chromium in the tanneries at Sialkot. They had significantly raised chromium levels in their biological fluids and adverse health effects due to enhanced oxidative stress and inflammatory changes.

Is Chromium an Essential Trace Element in Human Nutrition?

It has been recognized that chromium is an essential trace element associated with carbohydrate metabolism, and chromium deficiency causes an impaired glucose tolerance. Recently, however, Vincent et al. have reported that chromium is not an essential trace element. In the present report, the author evaluated the nutritional essentiality of chromium by reviewing several previous reports. In almost all previous reports, the chromium concentration in the animal feed used was higher than 0.1 μg/g, and it is difficult to consider that the experimental animals were in a low-chromium state. In addition, the amount of chromium administered to the animals for the improvement of glucose tolerance was at a pharmacological level, and corresponded to a level that far exceeded the human daily chromium intake (20 to 80 μg/day). On the other hand, recent research has clearly shown that feeding with a severely low-chromium diet (0.016 μg/g) does not impair glucose tolerance. The amount of chromium absorbed in humans estimated from chromium intake (20 to 80 μg/day), chromium absorption rate (1%), and urinary chromium excretion (<1 μg/day) is less than 1 μg/day, which is much lower than those of other essential trace elements. In addition, because there is an inconsistency between the chromium concentration in food and chromium intake, chromium intake seems to be dependent on chromium contamination during food processing and cooking. It is concluded that there is a high possibility that chromium is not an essential trace element.

Deferoxamine pretreatment prevents Cr(VI)-induced nephrotoxicity and oxidant stress: Role of Cr(VI) chelation

Deferoxamine (DFO) is a recognized iron chelator which has been shown to exert nephroprotection in models of toxic nephropathies. In the present work the potential protective effects of DFO against Cr(VI)-induced nephrotoxicity and oxidant stress were evaluated. Rats were injected with a single injection (15mg/kg, s.c.) of potassium dichromate (K2Cr2O7). DFO was given as a single i.p. injection 30min before K2Cr2O7 administration at three different doses (100, 200 and 400mg/kg). It was found that DFO pretreatment attenuated, in a dose-dependent way, K2Cr2O7-induced renal dysfunction and structural alterations evaluated by serum creatinine, blood urea nitrogen, creatinine clearance, proteinuria, plasma glutathione peroxidase activity, urinary excretion of N-acetyl-β-d-glucosaminidase and histological analyses. Furthermore, DFO prevented the K2Cr2O7-induced renal oxidant stress and the decrease in the activity of the antioxidant enzymes superoxide dismutase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase and catalase. Finally it was found that DFO, at 400mg/kg, decreases renal Cr(VI) content which prompted us to evaluate the potential Cr(VI) chelating properties of this compound. Indeed was found in an in vitro assay that DFO was an effective Cr(VI) chelator with an IC50 of 800μg. In additional groups of rats was found that DFO posttreatment was ineffective to attenuate K2Cr2O7-induced nephrotoxicity and renal oxidant stress. Furthermore, DFO was unable to modify urinary excretion of total chromium. The nephroprotective effect of DFO against Cr(VI)-induced nephrotoxicity and oxidant stress may be explained, at least partially, by the ability of DFO to chelate Cr(VI) and to attenuate renal Cr(VI) content. However, it cannot be excluded that the ability of DFO to chelate iron may also be involved in the protection observed in our study.

Increased insulin resistance is associated with increased urinary excretion of chromium in non-diabetic, normotensive Saudi adults

The role of trivalent chromium in improving glucose tolerance is well documented. Increased urinary chromium has been reported in type 2 diabetes mellitus, but it was not clear whether this had preceded diabetes mellitus, or was caused by it. Aim was to investigate the relationship between urinary chromium and the degree of insulin resistance in non-diabetic normotensive Saudi adults. 357 healthy adults aged 18–50 years were recruited randomly in a cross-sectional study design. Anthropometric and demographic information were taken. Insulin, glucose and free fatty acids were measured in fasting blood samples. Fasting urinary chromium and creatinine were also determined. Using modified QUICKI, subjects were labeled as high insulin resistant, or low insulin resistant. High insulin resistant subjects were matched for age and sex to low insulin resistant subjects. High insulin resistant subjects had higher mean BMI (p<0.001), mean waist circumference (p<0.01), and median urinary chromium (p<0.001) compared to low insulin resistant subgroup. Higher urinary chromium in high insulin resistant subgroup indicates a renal lesion leading to chromium deficiency and possibly diabetes mellitus eventually. Chromium supplementation might help to protect against the development of diabetes mellitus in this group of high insulin resistant non-diabetic Saudi individuals.

Histopathological and biochemical changes in rat thyroid following acute exposure to hexavalent chromium.

Chromium in hexavalent form is highly toxic and a known carcinogen, although its effects on thyroid structure and function are relatively unexplored. Workers in an industrial environment can be, at times, exposed to this form of chromium. The present study was, therefore, designed using laboratory rats as a model system to investigate the effect on thyroid structure and function following two acute intraperitoneal doses of 30 mg/kg b.w. potassium dichromate administered within 48 hours. The results showed that hypothalamic chromium concentration increased (p<0.05) while thyroid chromium concentration decreased (p<0.01).The excretion of chromium in urine increased (p<0.05). The treated thyroid sections revealed hyperplasia. Follicles were disorganized, clustered and collapsed, while some of them were fused. Interfollicular spaces widened. Morphometrical analysis showed significantly (p<0.001) increased number of follicles whereas the follicular size significantly decreased (p<0.001). Nuclei were regressed (p<0.001); nuclear shapes were irregular; round, oval and shrunken. The membrane on the apical as well as the basal lamina side showed disruption. Colloid retraction within the follicles was noticeable in some sections stained with Periodic acid Schiff (PAS). Serum free tetra-iodothyronine (FT4) and free tri-iodothyronine (FT3) levels decreased (p<0.01 and p<0.001, respectively), while serum thyroid stimulating hormone (TSH) concentration increased (p<0.01). Ultrastructural analysis showed disrupted basal laminae of the follicles, regressed nuclei and disrupted cell organelles. Acridine orange stained thyroid cells demonstrated excessive dead cells, whereas DNA fragmentation assay demonstrated percent decrease of hypothalamic, pituitary and thyroidal total DNA.

Tissue accumulation and urinary excretion of chromium in rats fed diets containing graded levels of chromium chloride or chromium picolinate

To attempt a risk assessment of the excess intake of trivalent chromium (Cr), tissue Cr accumulation and urinary Cr excretion were examined in weanling rats fed experimental diets containing graded levels of Cr chloride (CrCl3) or Cr picolinate (CrPic). Thirty-six male weanling 4-weeks-old Wistar rats were divided into six groups and fed a casein-based semi-purified diet (Cr content: <0.02 microg/g) supplemented with 1, 10, or 100 microg Cr/g as CrCl3 or CrPic for 28 days. Among the experimental groups, no significant difference was observed in body weight; however, supplementation of 100 microg Cr/g to the diets caused a significant low liver weight irrespective of the chemical species of Cr. Activities of serum aspartate aminotransferase and alanine aminotransferase were significantly elevated in rats given CrPic at 100 microg Cr/g. In the liver, kidney and femur, Cr accumulation increased with elevation of the dietary Cr level. No influence of the difference in the chemical species of supplemented Cr was observed in the liver and kidney, but CrCl3 caused significantly higher Cr accumulation than CrPic in the femur of rats given 100 microg Cr/g. Daily urinary Cr excretion elevated with the increase of the dietary Cr level. Rats given CrPic showed significantly higher daily urinary Cr excretion than those given CrCl3, particularly at a dietary Cr level of 100 microg/g. The rate of urinary Cr excretion in rats given CrPic was constant, irrespective of the dietary Cr level, but that of rats given CrCl3 fell with the increase of the dietary Cr level. These results indicate that the lowest adverse effect level of dietary Cr is less than 100 microg/g, irrespective of the chemical species of Cr.

Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A - Medical results

BackgroundThis study investigated the effect of oral dimercapto succinic acid (DMSA) therapy for children with autism spectrum disorders ages 3-8 years.MethodsPhase 1 involved 65 children who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo.ResultsDMSA greatly increased the excretion of lead, substantially increased excretion of tin and bismuth, and somewhat increased the excretion of thallium, mercury, antimony, and tungsten. There was some increase in urinary excretion of essential minerals, especially potassium and chromium. The Phase 1 single round of DMSA led to a dramatic normalization of RBC glutathione in almost all cases, and greatly improved abnormal platelet counts, suggesting a significant decrease in inflammation.ConclusionOverall, DMSA therapy seems to be reasonably safe, effective in removing several toxic metals (especially lead), dramatically effective in normalizing RBC glutathione, and effective in normalizing platelet counts. Only 1 round (3 days) was sufficient to improve glutathione and platelets. Additional rounds increased excretion of toxic metals.

Six-year results of a prospective study of metal ion levels in young patients with metal-on-metal hip resurfacings

We describe the findings at six years in an ongoing prospective clinicoradiological and metal ion study in a cohort of 26 consecutive male patients with unilateral Birmingham Hip Resurfacing arthroplasties with one of two femoral head sizes (50 mm and 54 mm). Their mean age was 52.9 years (29 to 67). We have previously shown an early increase in the 24-hour urinary excretion of metal ions, reaching a peak at six months (cobalt) and one year (chromium) after operation. Subsequently there is a decreasing trend in excretion of both cobalt and chromium. The levels of cobalt and chromium in whole blood also show a significant increase at one year, followed by a decreasing trend until the sixth year.