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CHROMIUM

 

Title

Oxidative stress, mitochondrial respiration, and glycemic control: clues from chronic supplementation with Cr3+ or As3+ to male Wistar rats.

Author

Cobo JM; Casti~neira M

Address

Facultad de Farmacia, Universidad de Alcal´a de Henares, Spain.

Source

Nutrition, 13(11-12):965-70 1997 Nov-Dec

Abstract

Multiple experiments in male Wistar rats were designed to clarify the role of mitochondrial dysfunction in the mechanisms of oxidative stress-related diseases and toxicity-induced pathologies. In this particular report, 21 male Wistar rats were supplemented ad libitum with either As3+ or Cr3+ salts in drinking water to assess insulin secretion patterns in vivo and in vitro, mitochondrial dysfunction, oxidative stress, liver damage, basal insulin, and glucose tolerance curves, among other parameters. Results were compared with a control group without any metal supplementation. The CrCl3 supplements were more invasive of metabolism and had a stronger effect on mitochondrial dysfunction than As3+, despite that both seem to use similar mechanisms of toxicity; viz.: binding to thiol or -SS- group in enzymes and proteins, and releasing oxidant species during their redox-cycling and metabolic activation processes, e.g., by cytochrome P450 in liver. Results support our aim to prove the influence of oxidative stress-induced mitochondrial dysfunction on glycemic control.

 

Title

Radiochromium distribution in thyroid and parathyroid deficiency.

Author

Lifschitz ML; Wallach S; Peabody RA; Verch RL; Agrawal R

Source

Am J Clin Nutr, 33(1):57-62 1980 Jan

Abstract

Body retention and tissue distribution of a 51chromium (Cr) tracer were studied in thyroparathyroidectomized (TPTX) rats and in TPTX rats after replacement with thyroxin, calcitonin, or parathyroid hormone. A tracer dose containing 1 ng Cr or less and 0.5 to 0.7 muCi of high specific activity 51Cr (Cr III) was injected intravenously in control, TPTX, and TPTX animals receiving hormone replacement. Three days later, the 51Cr content of the serum and various tissues was determined and the data were expressed as percent dose per milliliter or gram and as tissue: serum 51Cr ratios. TPTX resulted in a significant increase in total body 51Cr retention and 40 to 240% increases in serum and tissue 51Cr levels. Tissue:serum 51Cr ratios were uniformly depressed. Replacement with thyroxin completely or partially reversed these changes in all tissues studied except bone. Calcitonin and parathyroid hormone had no consistent effect on body, serum, or tissue 51Cr levels. These data, indicating that 51Cr distribution is influenced by thyroid hormone activity but not by calcitonin or parathyroid hormone, are compatible with the hypothesis that thyroid hormone controls cellular Cr transport.

Chromium update: examining recent literature 1997-1998.

Preuss HG, Anderson RA

In vivo effects of chromium.

Witmer C, Faria E, Park HS, Sadrieh N, Yurkow E, O'Connell S, Sirak A, Schleyer H

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

Lovkova MIa, Buzuk GN, Sokolova SM, Kliment'eva NI, Ponomareva SM, Shelepova OV, Vorotnitskaia IE

 

Sci Total Environ 2000 Apr 17;249(1-3):143-70

Experimental copper and chromium deficiency and additional molybdenum supplementation in goats. II. Concentrations of trace and minor elements in liver, kidneys and ribs: haematology and clinical chemistry.

Frank A, Danielsson R, Jones B

Department of Clinical Chemistry, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala. dr.a.frank@rocketmail.com

Since the mid-1980s a previously undescribed disease has affected moose in south-western Sweden. Investigations made to reveal evidence of a viral aetiology have proved unsuccessful. Trace element studies in apparently healthy moose shot during regular hunting suggested a trace element imbalance, with excessive molybdenum uptake causing secondary copper deficiency. The results also indicated a possible chromium deficiency. To verify this hypothesis, an experimental study was performed in male goats fed a semi-synthetic diet for 1.5 years. The animals were kept and treated in four groups: Controls, Cu-deficient group (group 1), Cr-deficient group (group 2), and combined Cu- and Cr-deficient group with additional supplementation of tetrathiomolybdate for 10 weeks at the end of the study (group 3). The present paper presents tissue contents of trace and minor elements, haematology and clinical chemical parameters. Feed consumption and weight development, as well as pathological and histopathological investigations, were also performed in this study, but these results are presented elsewhere. Changes in trace element concentrations were determined by comparing groups 1, 2 and 3 with the control group. Increased concentrations were observed for Al, Ca, Co, Fe, Mo, Pb, Se in the liver; for Al, Cd, Co, Cr, Mo in the kidneys; and for Mn and Mo in the ribs. Considerable accumulation of Mn in ribs seems to be a useful way to determine oxidative stress. Decreases in Mg and P in all organs and blood serum is characteristic of Cu deficiency and molybdenosis. Also the ratio of Ca/Mg was increased as the result of tissue lesions causing an intracellular increase in Ca and decrease in Mg. The trace element changes observed in group 1 were enhanced by the Mo supplementation in group 3, resulting in characteristic patterns, 'spectra' of changes. The alterations were not as remarkable in group 2 as in the two other groups. However, Cr deficiency considerably influenced Al, Co, V and to a smaller extent also Mn in ribs. In groups 1 and 2, only a few minor changes were detected in the haematological parameters, probably caused by increased adrenal activity after transportation of the animals. In group 3, severe anaemia was present but also a leukopenia. For the different clinical chemical parameters measured, all three groups showed changes, explained mainly by the altered activity of enzymes induced by trace element deficiencies and imbalance. Impaired carbohydrate and lipid metabolism was seen in groups 1 and 3, with increased concentrations of glucose, lactate and triglycerides in serum. Increased concentrations of total bilirubin were measured in all three groups (bile stasis was also seen post mortem). A considerably increased concentration of serum urea was found in group 3, although there were no indications of renal insufficiency or dehydration. Regarding hormones, a substantial decrease was seen in thyroxine (T4) in group 3 as a result of the molybdenosis, but a minor decrease was also seen in group 1. Insulin on the other hand showed increased levels in group 3--and especially in group 2 due to the Cr deficiency but also affected by the molybdenosis. As could be expected, Cu deficiency (groups 1 and 3) caused low levels of caeruloplasmin, secondarily affecting the Fe metabolism in these animals. Protein abnormalities, detected as altered electrophoretic patterns of serum proteins, were also seen mainly in group 3. The findings were also confirmed by multivariate data analysis, where PCA revealed the overall impact of the deficiencies, and PLS regression coefficients indicated the influence on the various analytes.

 

The following study shows that a weight gain will result if copper is adequate and chromium is deficient.

Sci Total Environ 2000 Apr 17;249(1-3):133-42

Experimental copper and chromium deficiency and additional molybdenum supplementation in goats. I. Feed consumption and weight development.

Frank A, Anke M, Danielsson R

Department of Clinical Chemistry, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala. dr.a.frank@rocketmail.com

Secondary Cu deficiency, Cr deficiency and molybdenosis were suggested causes of the 'mysterious' disease afflicting moose (Alces alces L.) in a region in south-west Sweden affected by acid rain. A model experiment with goats was performed to study the clinical chemical parameters, determine the tissue contents of trace and minor elements, to perform pathological and histopathological investigations and to compare the findings with those in moose disease. Twenty 3-month-old male goats were assigned to four dietary treatments (five animals each) in an experiment lasting for 20 months. The four groups in the study were: control group, Cu-deficient group (group 1), Cr-deficient group (group 2), and Cu- and Cr-deficient group (group 3). The animals were fed a basic semi-synthetic diet. At the end of the study the three surviving animals of group 3 were supplemented with additional tetrathiomolybdate (TTM) during the last 2 months. Feed consumption and weight development of the animals were monitored and are presented. The feed consumption of the two Cu-deficient groups of goats (group 1 and group 3) supported the previously described observations in copper deficiency in ruminants, e.g. decreased appetite and feed intake. A previously unreported effect of Cr deficiency in ruminants is now described in goats. Chromium deficiency at adequate Cu supplementation (group 2), caused increased lipid synthesis and a weight gain of 32 kg compared with that of the control group (20 kg). A possible explanation for this unexpected weight increase in only Cr deficiency is discussed. It is concluded that the feeding experiment does not support the hypothesis concerning the relation of Cr deficiency to the moose disease.

 

Curr Opin Clin Nutr Metab Care 1998 Nov;1(6):509-12

Chromium update: examining recent literature 1997-1998.

Preuss HG, Anderson RA

Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA.

Trivalent chromium is an essential nutrient required for sugar and fat metabolism. The majority of people eating typical Western diets consume less than the upper limit of the estimated safe and adequate daily dietary intake, which is set at 50-200 micrograms per day. Insufficient chromium intake is associated with signs and symptoms similar to those seen in diabetes and cardiovascular diseases. The efficacy of chromium in the general population relates to its prevention of deficiency or a reduction in the risk of chronic diseases. It is possible that doses above the estimated safe and adequate daily dietary intake are necessary for the treatment of certain chronic disease states. In a study performed in China, the use of 1000 micrograms of chromium per day (five times above the upper limit of the estimated safe and adequate daily dietary intake) was highly effective in relieving many of the symptomatic manifestations of type 2 diabetes mellitus, including a return of the HbA1C levels into the normal range. Most recent evidence strongly supports the conclusion that there is little fear of toxic reactions from chromium consumption. In addition to type 2 diabetes mellitus, chromium supplementation may be useful to direct overall weight decrements specifically towards fat loss with the retention of lean body mass and to ameliorate many manifestations of aging.

 

Izv Akad Nauk Ser Biol 1996 Sep-Oct;(5):552-64

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

[Article in Russian]

Lovkova MIa, Buzuk GN, Sokolova SM, Kliment'eva NI, Ponomareva SM, Shelepova OV, Vorotnitskaia IE

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

 

Ann Pharmacother 1998 Apr;32(4):428-31

Chromium picolinate toxicity.

Cerulli J, Grabe DW, Gauthier I, Malone M, McGoldrick MD

Nutrition Support, Division of Pharmacy Practice, Albany College of Pharmacy, NY 12208, USA.

OBJECTIVE: To describe a case of toxicity secondary to chronic ingestion of 6-12 times the recommended daily allowance of over-the-counter (OTC) chromium picolinate. CASE SUMMARY: A 33-year-old white woman presented with weight loss, anemia, thrombocytopenia, hemolysis, liver dysfunction (aminotransferase enzymes 15-20 times normal, total bilirubin 3 times normal), and renal failure (serum creatinine 5.3 mg/dL; blood urea nitrogen 152 mg/dL). She had ingested chromium picolinate 1200-2400 microg/d for the previous 4-5 months to enhance weight loss. The patient had chromium plasma concentrations 2-3 times normal. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome were ruled out by clinical findings, peripheral blood smears, and a bone marrow biopsy. The patient was managed with supportive measures and received blood product transfusions and hemodialysis. Hemolysis stabilized and liver function improved over 6 days. Liver function returned to normal prior to discharge. Renal function began to return on day 12 and her serum creatinine on discharge was 1.3 mg/dL. One year later, all laboratory values were within normal limits. DISCUSSION: Trivalent chromium is an essential trace element that is considered safe when ingested in normal quantities. Trivalent chromium compounds are used by patients to enhance weight loss, increase lean body mass, and/or improve glycemic control. Information regarding the toxicity of chromium picolinate is limited. CONCLUSIONS: Chromium supplements may cause serious renal impairment when ingested in excess. Medication histories should include attention to the use of OTC nutritional supplements often regarded as harmless by the public and lay media.

 

Toxicology 1997 Feb 14;117(1):45-53

Biphasic effects of chromium compounds on catecholamine secretion from bovine adrenal medullary cells.

Liu PS, Lin MK

Department of Microbiology, Soochow University, Taipei, Taiwan, Peoples Republic of China.

CrO3 was found to affect norepinephrine release in a biphasic manner: at concentrations above 100 microM, it inhibited, while at concentrations below 10 microM, it enhanced DMPP- and high K+-induced [3H]norepinephrine (NE) release from bovine adrenal medullary cells. Similar effects were found for K2Cr2O7. CrO3 inhibited the 45Ca2+ uptake induced by DMPP and high K+, suggesting that the voltage-gated Ca2+ channels are possible sites of the inhibitory action of CrO3. CrCl3, possessing a trivalent state in contrast to the hexavalent states of CrO3, K2Cr2O7, inhibited DMPP-induced [3H] release and inhibited, to a lesser extent, high K+-induced [3H]-NE release, suggesting that nicotinic receptors are also possible sites of Cr3+ action. In medullary cells permeabilized with digitonin, both CrO3 and CrCl3 induced [3H]-NE release from cells preloaded with [3H]-NE. In intact cells, CrO3 but not CrCl3 enhanced secretagogue-induced [3H]-NE release and entered into the cells as demonstrated by fluorescence quenching experiments. These results suggest that chromium compounds can induce catecholamine secretion after entering the cytoplasm. The enhancement of norepinephrine release induced by chromium ions appears to be due to interference with the intracellular functions of Ca2+ in the cytoplasm.

Chromium Supplementation Lowers Glucose, Lipid Levels in Elderly Diabetics

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WASHINGTON (Reuters Health) Nov 20, 2000 - Dietary supplementation with chromium decreased glucose and lipid levels in type 2 diabetics enrolled in an active rehabilitation program, Dr. Haim Rabinovitz reported here in a poster presentation at a meeting of the Gerontological Society of America.

Dr. Rabinovitz, of Shmuel Harofe Hospital, Tel-Aviv, Israel, and colleagues studied the effects of chromium picolinate supplementation on 39 diabetic subjects, average age 73, who were recovering from a stroke or hip fracture. Although the effects of chromium on diabetics have been studied by other researchers, few studies have looked at the effect of chromium in an older population, Dr. Rabinovitz told Reuters Health.

In addition to receiving standard diabetes treatment, all subjects were given 200 mcg of chromium twice a day for 3 weeks. Participants were placed on a low-sugar diet of 1500 calories a day. Blood samples, dietary intake, and anthropometric data were collected before and after supplementation.

The researchers found a significant decrease in the subjects' fasting blood glucose levels, from an average of 189 mg/dL to 150 mg/dL. Their hemoglobin A1c levels also improved, falling from an average of 8.15 to 7.58. Total cholesterol dropped from 225.26 mg/dL to 211.42 mg/dL. Triglyceride levels fell from 152 mg/dL to 136 mg/dL.

Chromium appears to work by increasing the sensitivity of the patients' insulin receptors, so they are able to use the insulin more effectively, Dr. Rabinovitz explained. There have been no side effects from it, he added.