Ultrastructural damage in chromium picolinate-treated cells: a TEM study

Manygoats, K.; Yazzie, Monica; Stearns, Diane M.

doi:10.1007/s00775-002-0357-z

Cited by 74 publications

(42 citation statements)

References 28 publications

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“…Our results show that severe GSH loss in Clara cells causes substantial swelling, actin cytoskeleton disruptions, and plasma membrane blebbing. These types of cellular changes have been reported in cells exposed to various toxicants and may represent a generic response of the cell to GSH loss and/or oxidative stress seen in the earliest stages of cell death (Jewell et al, 1982;Reed and Fariss, 1984;Mirabelli et al, 1988;Zahrebelski et al, 1995;Manygoats et al, 2002). Necrotic cell death was only observed in Clara cells exposed to NA, where GSH loss and protein adduct formation are known to occur (Buckpitt et al, 2002).…”

Section: Depletion Of Gsh In Clara Cellmentioning

confidence: 77%

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Consequences of Abrupt Glutathione Depletion in Murine Clara Cells: Ultrastructural and Biochemical Investigations into the Role of Glutathione Loss in Naphthalene Cytotoxicity

Phimister¹,

Williams²,

Winkle

et al. 2005

J Pharmacol Exp Ther

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Glutathione plays many critical roles within the cell, including offering protection from reactive chemicals. The bioactivated toxicant naphthalene forms chemically reactive intermediates that can deplete glutathione and covalently bind to cellular proteins. Naphthalene selectively injures the nonciliated epithelial cells of the intrapulmonary airways (i.e., Clara cells). This study attempted to define what role glutathione loss plays in naphthalene cytotoxicity by comparing Swiss-Webster mice treated with naphthalene with those treated with the glutathione depletor diethylmaleate. High-resolution imaging techniques were used to evaluate acute changes in Clara cell ultrastructure, membrane permeability, and cytoskeleton structure. A single dose of either diethylmaleate (1000 mg/kg) or naphthalene (200 mg/kg) caused similar glutathione losses in intrapulmonary airways (Ͻ20% of control). Diethylmaleate did not increase membrane permeability, disrupt mitochondria, or lead to cell death-hallmark features of naphthalene cytotoxicity. However, diethylmaleate treatment did cause Clara cell swelling, plasma membrane blebs, and actin cytoskeleton disruptions similar to naphthalene treatment. Structural changes in mitochondria and Golgi bodies also were noted. Changes in ATP levels were measured as an indication of overall cell function, in isolated airway explants incubated with diethylmaleate, naphthalene, or naphthalene metabolites in vitro. Only the reactive metabolites of naphthalene caused significant ATP losses. Unlike the lethal injury caused by naphthalene, the disruptive cellular changes associated with glutathione loss from diethylmaleate seemed to be reversible after recovery of glutathione levels. This suggests that glutathione depletion may be responsible for some aspects of naphthalene cytotoxicity, but it is not sufficient to cause cell death without further stresses.

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Section: Depletion Of Gsh In Clara Cellmentioning

confidence: 77%

“…Studies in hepatocytes have shown a similar progression of cellular degeneration in response to reactive toxicants (Zahrebelski et al, 1995;Manygoats et al, 2002). GSH loss has been implicated in many of these cellular responses to toxicants (Jewell et al, 1982;Reed and Fariss, 1984;Mirabelli et al, 1988).…”

mentioning

confidence: 96%

Consequences of Abrupt Glutathione Depletion in Murine Clara Cells: Ultrastructural and Biochemical Investigations into the Role of Glutathione Loss in Naphthalene Cytotoxicity

Phimister¹,

Williams²,

Winkle

et al. 2005

J Pharmacol Exp Ther

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“…20 In vitro tests showed that apoptosis of osteosarcoma cells occurred rapidly 6 hours after one hour of thermotherapy at 43.5°C. 21 Apoptosis is a process of active suicide of cells and is a form of planned cell death. Our flow cytometry analysis showed the same phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Biocompatibility of magnetic Fe3O4 nanoparticles and their cytotoxic effect on MCF-7 cells

Chen

Tang²,

Li³

et al. 2012

IJN

144

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Background:The objective of this study was to evaluate the synthesis and biocompatibility of Fe 3 O 4 nanoparticles and investigate their therapeutic effects when combined with magnetic fluid hyperthermia on cultured MCF-7 cancer cells. Methods: Magnetic Fe 3 O 4 nanoparticles were prepared using a coprecipitation method. The appearance, structure, phase composition, functional groups, surface charge, magnetic susceptibility, and release in vitro were characterized by transmission electron microscopy, x-ray diffraction, scanning electron microscopy-energy dispersive x-ray spectroscopy, and a vibrating sample magnetometer. Blood toxicity, in vitro toxicity, and genotoxicity were investigated. Therapeutic effects were evaluated by MTT [3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide] and flow cytometry assays. Results: Transmission electron microscopy revealed that the shapes of the Fe 3 O 4 nanoparticles were approximately spherical, with diameters of about 26.1 ± 5.2 nm. Only the spinel phase was indicated in a comparison of the x-ray diffraction data with Joint Corporation of Powder Diffraction Standards (JCPDS) X-ray powder diffraction files. The O-to-Fe ratio of the Fe 3 O 4 was determined by scanning electron microscopy-energy dispersive x-ray spectroscopy elemental analysis, and approximated pure Fe 3 O 4 . The vibrating sample magnetometer hysteresis loop suggested that the Fe 3 O 4 nanoparticles were superparamagnetic at room temperature. MTT experiments showed that the toxicity of the material in mouse fibroblast (L-929) cell lines was between Grade 0 to Grade 1, and that the material lacked hemolysis activity. The acute toxicity (LD 50 ) was 8.39 g/kg. Micronucleus testing showed no genotoxic effects. Pathomorphology and blood biochemistry testing demonstrated that the Fe 3 O 4 nanoparticles had no effect on the main organs and blood biochemistry in a rabbit model. MTT and flow cytometry assays revealed that Fe 3 O 4 nano magnetofluid thermotherapy inhibited MCF-7 cell proliferation, and its inhibitory effect was dose-dependent according to the Fe 3 O 4 nano magnetofluid concentration. Conclusion: The Fe 3 O 4 nanoparticles prepared in this study have good biocompatibility and are suitable for further application in tumor hyperthermia.

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“…Randomized studies with results on glucose, insulin, and/or A1C were collected by Althuis et al (10) in their review. Reasons for the inconclusive findings are that too few trials in patients with diabetes have been conducted to allow conclusive findings (three trials with a total of 38 subjects).Furthermore, in recent years, the safety of chromium supplements has been called into question because of mixed results in studies investigating the mutagenicity of chromium picolinate in vitro (12)(13)(14). Although toxic effects were reported in neither the systematic reviews (10,11) nor in the study of Anderson et al (9), chromium picolinate was banned by the Food Standards Agency until December 2004 (15).…”

mentioning

confidence: 99%

“…Furthermore, in recent years, the safety of chromium supplements has been called into question because of mixed results in studies investigating the mutagenicity of chromium picolinate in vitro (12)(13)(14). Although toxic effects were reported in neither the systematic reviews (10,11) nor in the study of Anderson et al (9), chromium picolinate was banned by the Food Standards Agency until December 2004 (15).…”

mentioning

confidence: 99%

Chromium Treatment Has No Effect in Patients With Type 2 Diabetes in a Western Population

Kleefstra

Houweling²,

Bakker

et al. 2007

Diabetes Care

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OBJECTIVE -Chromium treatment has been reported to improve glycemic control in patients with type 2 diabetes. However, concern exists about the possible toxic effects of chromium picolinate. The aim of this study was to determine the effect of chromium treatment in the form of chromium yeast on glycemic control in a Western population of patients with type 2 diabetes who were being treated with oral hypoglycemic agents.RESEARCH DESIGN AND METHODS -In this 6-month, double-blind study, patients with moderate glycemic control, being treated with oral hypoglycemic agents, were randomly assigned to receive either a placebo or treatment with 400 g of chromium daily in the form of chromium yeast. The primary efficacy parameter was a change in A1C. Secondary end points were changes in lipid profile, BMI, blood pressure, body fat, and insulin resistance.RESULTS -No differences were found for the change in A1C between the intervention and placebo groups, nor were any differences found between the groups for the secondary end points.CONCLUSIONS -There is no evidence that chromium in the form of chromium yeast is effective in improving glycemic control in Western patients with type 2 diabetes who are taking oral hypoglycemic agents. Diabetes Care 30:1092-1096, 2007T ype 2 diabetes is a chronic, progressive illness that causes considerable morbidity and premature mortality (1,2). The worldwide prevalence of type 2 diabetes is high and is increasing steadily (3). The majority of patients are insulin resistant (4). Although these patients may be treated with well-established hypoglycemic agents, studying alternative treatment options directed toward improving insulin sensitivity is important.For many decades, we have known that chromium plays a role in glucose metabolism, and, as early as 1957, it was already being referred to as "a glucose tolerance factor" (5). In vitro and animal studies have shown that chromium improves insulin resistance (6,7). One of the intracellular proteins that influences the insulin receptor is the oligopeptide apolipoprotein low-molecular weight chromium-binding substance (Apochromomodulin) (7). This peptide has the ability to increase tyrosine kinase activity eightfold, depending on the chromium concentration (8), thus strengthening the idea that chromium plays an influential role in glucose metabolism (5).The largest study (n ϭ 180) to date investigating the effect of chromium in patients with type 2 diabetes was published by Anderson et al. (9). They found that the A1C of Chinese patients treated with 1,000 g of chromium in the form of chromium picolinate decreased almost 2 percentage points compared with a placebo group after 4 months. However, two systematic reviews that addressed the effects of chromium on glycemic control concluded that, on the basis of the currently available data, the effects of chromium on glycemic control are inconclusive (10,11). Randomized studies with results on glucose, insulin, and/or A1C were collected by Althuis et al. (10) in their review. Reasons for the inconcl...

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Ultrastructural damage in chromium picolinate-treated cells: a TEM study

Cited by 74 publications

References 28 publications

Consequences of Abrupt Glutathione Depletion in Murine Clara Cells: Ultrastructural and Biochemical Investigations into the Role of Glutathione Loss in Naphthalene Cytotoxicity

Consequences of Abrupt Glutathione Depletion in Murine Clara Cells: Ultrastructural and Biochemical Investigations into the Role of Glutathione Loss in Naphthalene Cytotoxicity

Biocompatibility of magnetic Fe3O4 nanoparticles and their cytotoxic effect on MCF-7 cells

Chromium Treatment Has No Effect in Patients With Type 2 Diabetes in a Western Population

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