| 1. |
- Augustsson, Anna, et al.
(author)
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Trace and major elements in food supplements of different origin : implications for daily intake levels and health risks
- 2021
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In: Toxicology reports. - : Elsevier. - 2214-7500. ; 8, s. 1067-1080
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Journal article (peer-reviewed)abstract
- As the use of food supplements increases, voices are being raised questioning the safety of these products. As a contribution to understanding the trace and major elemental composition of food supplements and their potential health risks, this study presents concentrations of 71 elements in 138 supplements, categorised into synthetic products and three groups of products with natural ingredients. Concentrations were converted into average daily doses (ADDs) and compared to tolerable daily intakes (TDIs). For elements where we found significant ADDs relative to the TDI a comparison was also made to the normal dietary intake. Our main findings are that: 1) Most elements display highly variable concentrations in food supplements; more so than in normal foodstuff; 2) For ten of the analysed elements some products rendered ADDs > 50% of the TDI. Half of the elements were essential (Fe, Mn, Se, Mo, Zn), and as such motivated in food supplements. The other half (As, Pb, Cd, Al, Ni) represent non-essential and highly toxic elements, where the occurrence in food supplements ought to be viewed as contamination. Although none of these toxic metals were declared on any product’s table of content, several products gave high ADDs - in several cases even exceeding the TDIs; 3) The risk of reaching high ADDs for the toxic elements is strongly associated with products that contain marine ingredients (e.g. algae, mussels etc), and to some degree products of terrestrial plant-based origin. The health of consumers would benefit if food regulatory frameworks were updated to better address the risks of food supplements occasionally being contaminated with different toxic metals, for example by setting maximum permissible concentrations for a longer list of elements.
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| 2. |
- Bodin, Johanna, et al.
(author)
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Exposure to bisphenol A, but not phthalates, increases spontaneous diabetes type 1 development in NOD mice
- 2015
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In: Toxicology Reports. - : Elsevier BV. - 2214-7500. ; 2, s. 99-110
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Journal article (peer-reviewed)abstract
- Type 1 diabetes mellitus (T1DM) is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA) accelerates the spontaneous development of diabetes in non-obese diabetic (NOD) mice. Here, we hypothesized that oral exposure to a mixture of the endocrine disruptors BPA and phthalates, relevant for human exposure, would accelerate diabetes development compared to BPA alone. NOD mice were exposed to BPA (1 mg/l), a mixture of phthalates (DEHP 1 mg/l, DBP 0.2 mg/l, BBP 10 mg/l and DiBP 20 mg/l) or a combination of BPA and the phthalate mixture through drinking water from conception and throughout life. Previous observations that BPA exposure increased the prevalence of diabetes and insulitis and decreased the number of tissue resident macrophages in pancreas were confirmed, and extended by demonstrating that BPA exposure also impaired the phagocytic activity of peritoneal macrophages. None of these effects were observed after phthalate exposure alone. The phthalate exposure in combination with BPA seemed to dampen the BPA effects on macrophage number and function as well as diabetes development, but not insulitis development. Exposure to BPA alone or in combination with phthalates decreased cytokine release (TNFα, IL-6, IL-10, IFNγ, IL-4) from in vitro stimulated splenocytes and lymph node cells, indicating systemic changes in immune function. In conclusion, exposure to BPA, but not to phthalates or mixed exposure to BPA and phthalates, accelerated diabetes development in NOD mice, apparently in part via systemic immune alterations including decreased macrophage function.
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| 3. |
- de Ávila, Renato Ivan, et al.
(author)
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Adjuvants in fungicide formulations can be skin sensitizers and cause different types of cell stress responses
- 2022
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In: Toxicology Reports. - : Elsevier BV. - 2214-7500. ; 9, s. 2030-2041
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Journal article (peer-reviewed)abstract
- New approaches based on -omics technologies can identify biomarkers and processes regulated in response to xenobiotics, and thus support toxicological risk assessments. This is vital to meet the challenges associated with “cocktail effects”, i.e. combination effects of chemicals present simultaneously in a product, our environment, and/or our body. For plant protection products (PPPs), investigations largely focus on active ingredients such as herbicides and fungicides. In this study, we have analyzed agricultural chemicals, two surfactants (poly(oxy-1,2-ethanediyl), alpha-sulfo-omega-[2,4,6-tris(1-phenylethyl)phenoxy]-, ammonium salt, POL; N,N-dimethylcapramide, NND), and one preservative, 1,2-benzisothiazol-3(2 H)-one (BEN) used as adjuvants in PPPs, and further three fungicide PPPs, Proline EC 250, Shirlan, Folicur Xpert, containing the adjuvants, and other major individual constituents (fluazinam (FLU), prothioconazole (PRO), tebuconazole (TEB)) as well as defined mixtures (“mixes”) thereof using several in vitro approaches. All investigated single agricultural chemicals were predicted as skin sensitizers using an in vitro transcriptomic assay based on a dendritic cell model. For selected chemicals and mixes, also skin sensitization potency was predicted. The preservative BEN induced significant changes in cytokine secretion and dendritic cell activation marker CD86 expression. The surfactant NND changed cytokine secretion only and the POL only affected CD86 expression. Proteomic analyses revealed unique response profiles for all adjuvants, an oxidative stress pattern response in BEN-treated cells, and differentially abundant proteins associated with cholesterol homeostasis in response to POL. In summary, we find responses to agricultural chemicals and products consistent with the dendritic cell model reacting to chemical exposure with oxidative stress, ER stress, effects on autophagy, and metabolic changes especially related to cholesterol homeostasis. After exposure to certain mixes, novel proteins or transcripts were differentially expressed and these were not detected for any single constituents, supporting the occurrence of cocktail effects. This indicates that all chemicals in a PPP can contribute to the toxicity profile of a PPP, including their skin sensitizing/immunotoxic properties.
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| 4. |
- Malakpour Permlid, Atena, et al.
(author)
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A Novel 3D Polycaprolactone High-Throughput System for Evaluation of Toxicity in Normoxia and Hypoxia
- 2021
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In: Toxicology Reports. - : Elsevier BV. - 2214-7500. ; 8, s. 627-635
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Journal article (peer-reviewed)abstract
- Two-dimensional (2D) culturing of cancer cells has been indispensable for the development of anti-cancer drugs. Drug development, however, is lengthy and costly with a high attrition rate, calling to mind that 2D culturing does not mimic the three-dimensional (3D) tumour microenvironment in vivo. Thus, began the development of 3D culture models for cancer research. We have constructed a 3D 96-well plate using electrospun fibres made of biocompatible polycaprolactone (PCL). Finely-cut PCL fibre pieces in water/ethanol solution was pipetted to the wells of hydrophobic 96-well plates. A fibrous network of approximately 200 µm thickness and high porosity was formed after crosslinking and drying. Human JIMT-1 breast cancer cells and fibroblasts were seeded into the network. Confocal microscopy shows that the cells grow throughout the fibre network. The toxicity of paclitaxel and an experimental salinomycin analogue was assessed and compared in 2D and 3D cultures incubated under conditions of normoxia and hypoxia often found in tumours. The toxicity of both compounds is lower when the cells are cultured in 3D compared to 2D when cultured in either normoxia or hypoxia. We conclude that our 96-well assay is a cost-efficient tool that may be used for high-throughput pre-clinical screening of potential anti-cancer compounds.
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| 5. |
- Murugesu, Suganya, et al.
(author)
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Toxicity study on Clinacanthus nutans leaf hexane fraction using Danio rerio embryos
- 2019
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In: Toxicology reports. - : ELSEVIER. - 2214-7500. ; 6, s. 1148-1154
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Journal article (peer-reviewed)abstract
- Clinacanthus nutans, an herbal shrub belonging to the Acanthaceae family, is traditionally used as a functional food to treat various ailments in Malaysia and Indonesia. Although the polar fraction of this plant shows nontoxic effect, the toxicity of the non-polar extract is not reported so far. The present study aimed to assess the toxic effect and determine the lethal concentration of this non-polar fraction using zebrafish embryos. The n-hexane fraction was partitioned from the crude extract of C. nutans obtained using 80% methanolic solution. After spawning of the adult male and female zebrafish, the eggs were collected, transferred into a 96-well plate and incubated with the n-hexane fraction at concentrations of 15.63 mu g/ml, 31.25 mu g/ml, 62.5 mu g/ml, 125 mu g/ml, 250 mu g/ml and 500 mu g/ml in 2% DMSO. The survival and sublethal endpoint were assessed, the mortality and hatchability rates were calculated based on microscopic observation, while the heartbeat rate was measured using DanioScope software. The median lethal concentration (LC50) of the C. nutans n-hexane fraction, which was determined using probit analysis, was calculated to be 75.49 mu g/mL, which is harmful. Moreover, gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of palmitic acid, phytol, hexadecanoic acid, 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol and stigmasterol in the n-hexane fraction.
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| 6. |
- Nasi, A, et al.
(author)
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Reactive oxygen species as an initiator of toxic innate immune responses in retort to SARS-CoV-2 in an ageing population, consider N-acetylcysteine as early therapeutic intervention
- 2020
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In: Toxicology reports. - : Elsevier Inc.. - 2214-7500. ; 7, s. 768-771
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Journal article (peer-reviewed)abstract
- During the current COVID-19 pandemic, a need for evaluation of already available drugs for treatment of the disease is crucial. Hereby, based on literature review from the current pandemic and previous outbreaks with corona viruses we analyze the impact of the virus infection on cell stress responses and redox balance. High levels of mortality are noticed in elderly individuals infected with SARS-CoV2 and during the previous SARS-CoV1 outbreak. Elderly individuals maintain a chronic low level of inflammation which is associated with oxidative stress and inflammatory cytokine production, a condition that increases the severity of viral infections in this population. Coronavirus infections can lead to alterations of redox balance in infected cells through modulation of NAD + biosynthesis, PARP function along with altering proteasome and mitochondrial function in the cell thereby leading to enhanced cell stress responses which further exacerbate inflammation. ROS production can increase IL-6 production and lipid peroxidation resulting in cell damage. Therefore, early treatment with anti-oxidants such as NAC during COVID-19 can be a way to bypass the excessive inflammation and cell damage that lead to severe infection, thus early NAC as intervention should be evaluated in a clinical trial setting.
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| 7. |
- Rafnsdóttir, Ólöf Birna, et al.
(author)
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A new animal product free defined medium for 2D and 3D culturing of normal and cancer cells to study cell proliferation and migration as well as dose response to chemical treatment
- 2023
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In: Toxicology Reports. - 2214-7500. ; 10, s. 509-520
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Journal article (peer-reviewed)abstract
- Cell culturing methods are increasingly used to reduce and replace the use of live animals in biomedical research and chemical toxicity testing. Although live animals are avoided when using cell culturing methods, they often contain animal-derived components of which one of the most commonly used is foetal bovine serum (FBS). FBS is added to cell culture media among other supplements to support cell attachment/spreading and cell proliferation. The safety, batch-to-batch variation, and ethical problems with FBS are acknowledged and therefore world-wide efforts are ongoing to produce FBS free media. Here, we present the composition of a new defined medium with only human proteins either recombinant or derived from human tissues. This defined medium supports long-term culturing/routine culturing of normal cells and of cancer cells, and can be used for freezing and thawing of cells, i.e. for cell banking. Here, we show for our defined medium, growth curves and dose response curves of cells grown in two and three dimensions, and applications such as cell migration. Cell morphology was studied in real time by phase contrast and phase holographic microscopy time-lapse imaging. The cell lines used are human cancer-associated fibroblasts, keratinocytes, breast cancer JIMT-1 and MDA-MB-231 cells, colon cancer CaCo-2 cells, and pancreatic cancer MiaPaCa-2 cells as well as the mouse L929 cell line. In conclusion, we present the composition of a defined medium without animal-derived products which can be used for routine culturing and in experimental settings for normal cells and for cancer cells, i.e. our defined medium provides a leap towards a universal animal product free cell culture medium.
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| 8. |
- Salomonsson, Matilda Lampinen, et al.
(author)
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Seafood sold in Sweden contains BMAA : A study of free and total concentrations with UHPLC-MS/MS and dansyl chloride derivatization
- 2015
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In: Toxicology reports. - : Elsevier BV. - 2214-7500. ; 2, s. 1473-1481
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Journal article (peer-reviewed)abstract
- β-N-Methylamino-l-alanine (BMAA) is a potential neurotoxin associated with the aquatic environment. Validated analytical methods for the quantification of both free and total concentrations of BMAA were used in an investigation of seafood purchased from different grocery stores in Uppsala, Sweden. The analysis was performed using ultra high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI–MS/MS) and detection of BMAA as a dansyl derivate. The determined concentrations of free BMAA (after a simple trichloroacetic acid extraction) in mussels and scallops were up to 0.46 μg g−1 wet homogenate. The total BMAA (after hydrochloric acid hydrolysis) levels were between 0.29 and 7.08 μg g−1 wet mussel homogenate. The highest concentration of total BMAA was found in imported cooked and canned mussels which contained about ten times the quantity of BMAA measured in domestic cooked and frozen mussels. In this study it was also concluded that BMAA could be detected in seafood origin from four different continents. The risks associated with human exposure to BMAA through food are unknown today. However, the results of this study show that imported seafood in Sweden contain BMAA, indicating that this area needs more investigation, including a risk assessment regarding the consumption of e.g., mussels, scallops and crab.
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| 9. |
- Schwalfenberg, Gerry, et al.
(author)
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Heavy metal contamination of prenatal vitamins
- 2018
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In: Toxicology reports. - : Elsevier. - 2214-7500. ; 5, s. 390-395
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Journal article (peer-reviewed)abstract
- Prenatal vitamins are often consumed daily during gestation and postnatally for up to 18–24 months with the belief that supplementation achieves better outcomes. Detrimental effects of gestational exposure to adverse chemical agents are gathering increasing attention. This study was designed to assess toxic element contamination in prenatal supplements.Twenty-six commonly used prenatal vitamin brands including one prescription brand were collected from Canadian health-food outlets and pharmacies, and tested for toxic element contamination. Results were compared to established endpoints.All samples contained Lead with average amounts being (0.535 μgm), 20/51 samples exceeded established standards for lead toxicity (0.50 μgm/day), with one sample yielding 4. μgm/day. Three samples registered inorganic arsenic levels above acceptable limits. Cadmium levels did not exceed current standards. Toxic elements such as Aluminum, Nickel, Titanium and Thallium were detected in all samples.Cumulative intake of prenatal supplement over many months may constitute a significant source of toxic element exposure to the mother and offspring. With several samples exceeding known standards for gestational toxic element exposure, guidelines for routine monitoring and reporting are required. In keeping with recommendations from the International Federation of Obstetrics and Gynecology, industry regulation would be welcomed to protect expectant mothers and their vulnerable offspring.
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| 10. |
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