| 1. |
- Ohlsson, Åsa, et al.
(författare)
-
Mixture effects of dietary flavonoids on steroid hormone synthesis in the human adrenocortical H295R cell line
- 2010
-
Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 48, s. 3194-3200
-
Tidskriftsartikel (refereegranskat)abstract
- Humans are exposed to a mixture of dietary flavonoids with a variety of potential beneficial and harmful effects. Flavonoids are endocrine disruptors, acting both at receptor level and by interfering with steroid hormone synthesis. Due to a high dietary intake and the potential to cause mixture effects, assessment of combined exposure of flavonoids is required. We have studied effects on cortisol, aldosterone, testosterone and oestradiol secretion of the individual isoflavones daidzein and genistein, the flavone apigenin and the mixture of the three flavonoids in human adrenocortical H295R cells. The most vulnerable targets of the flavonoids were the secretion of cortisol and testosterone, which were inhibited by daidzein and genistein with IC(50) values below 1 mu M. An equimolar mixture of the flavonoids caused inhibition of cortisol, aldosterone and testosterone secretion in an additive manner. The observed mixture effect was described well by both concentration addition (CA) and independent action (IA) prediction models. Both prediction models underestimated the effect on oestradiol secretion. We conclude that the three flavonoids exhibit specific effects on steroid hormone secretion. A mixture of the flavonoids caused additive effects emphasizing the need to assess flavonoids together as a group. The prediction models are valuable tools for mixture assessment. (C) 2010 Elsevier Ltd. All rights reserved.
|
|
| 2. |
- Ohlsson, Åsa, et al.
(författare)
-
Mixture effects of imidazole fungicides on cortisol and aldosterone secretion in human adrenocortical H295R cells
- 2010
-
Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 275, s. 21-28
-
Tidskriftsartikel (refereegranskat)abstract
- Exposure to chemicals commonly occurs in the form of mixtures. Methods and models are required to analyze and predict the effect of mixtures in order to improve risk assessment. The steroidogenesis and hormone production of the adrenal gland is a sensitive target for endocrine-disrupting chemicals including imidazoles. Here, we exposed human adrenocortical H295R cells to the individual imidazole fungicides prochloraz, ketoconazole, imazalil and their mixtures and analyzed the effects on secretion of cortisol and aldosterone and the effects on steroidogenic gene expression.The individual imidazole fungicides prochloraz, ketoconazole and imazalil and their mixtures inhibited cortisol secretion in a similar monotonic dose-response pattern with an EC50 value of approximately 0.1 mu M. Aldosterone secretion, in contrast, displayed a biphasic dose-response, with low-dose stimulation of up to maximum twofold and high-dose inhibition. Biphasic dose-responses were found following prochloraz and ketoconazole exposure and their mixtures, but not following imazalil exposure. The inhibition of cortisol secretion was equally well predicted with the concentration addition (CA) and independent action (IA) models, while the biphasic aldosterone response was partially predicted by a modified CA model and not predicted well by a modified IA model. Changes in expression levels of steroidogenic genes could not conclusively explain the different effects on the two hormone endpoints or the different specificities of the imidazoles. We conclude that single imidazoles and mixtures have specific effects on adrenal hormone secretion. These effects can only partly be predicted using current models and need to be further analyzed in terms of in vivo relevance and human risk assessment. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
|
|
| 3. |
- Oskarsson, Hanna, 1983-
(författare)
-
Pharmaecological perspectives : Exposure studies using coastal Baltic Sea organisms
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis investigates the effects of pharmaceutical substances on coastal Baltic Sea organisms. Despite an increasing awareness of the occurrence of pharmaceuticals in various aquatic compartments, current knowledge of their possible effects on non-target organisms is limited. Especially scarce is the knowledge concerning possible long-term effects, mixture-effects, effects on non-standard test organisms and indirect effects from interactions among organisms. Also the environmental fate, availability and distribution of pharmaceuticals between sediment, water and biota is only rarely investigated.The aim of this thesis was therefore to investigate the biological effects of pharmaceuticals, and their distribution in organisms of a coastal Baltic Sea community. In four studies, blue mussels, amphipods and macroalgae were exposed to pharmaceuticals in laboratory experiments. The effects from exposure, as well as recovery from the same, were studied on different physiological variables. With increasing complexity of experiment designs, the tested substances were found to affect aquatic organisms from different hierarchical levels both through direct negative effects, as well as through indirect positive effects within model communities. Moreover, the studies showed that the organisms were affected by exposure to environmentally relevant concentrations, but also that exposed organisms could recover from the exposure. Effects from pharmaceutical mixtures occurred in lower concentrations than effects from single pharmaceutical substances, and high internal concentrations of two pharmaceuticals – diclofenac and propranolol – were detected in exposed organisms.The detected effects and the uptake of pharmaceuticals in biota demonstrate a possible problem for aquatic environments, but especially for the Baltic Sea, since this is a naturally sensitive ecosystem with low species diversity, low functional redundancy and a history of heavy pollution.
|
|
| 4. |
- Ovesen, Rikke Gleerup, et al.
(författare)
-
Biomedicine in the environment : Cyclotides constitute potent natural toxins in plants and soil bacteria
- 2011
-
Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 30:5, s. 1190-1196
-
Tidskriftsartikel (refereegranskat)abstract
- Bioactive compounds produced by plants are easily transferred to soil and water and may cause adverse ecosystem effects. Cyclotides are gene-encoded, circular, cystine-rich mini-proteins produced in Violaceae and Rubiaceae in high amounts. Based on their biological activity and stability, cyclotides have promising pharmaceutical and agricultural applications. We report the toxicity of the cyclotides: kalata B1, kalata B2, and cycloviolacin O2 extracted from plants to green algae (Pseudokirchneriella subcapitata), duckweed (Lemna minor L.), lettuce (Lactuca sativa L.), and bacteria extracted from soil measured as [3H]leucine incorporation. Quantification by liquid chromatography-mass spectrometry demonstrated up to 98% loss of cyclotides from aqueous solutions because of sorption to test vials. Sorption was prevented by adding bovine serum albumin (BSA) to the aqueous media. Cyclotides were toxic to all test organisms with EC50 values of 12 through 140 µM (algae), 9 through 40 µM (duckweed), 4 through 54 µM (lettuce), and 7 through 26 µM (bacteria). Cycloviolacin O2 was the most potent cyclotide in all assays examined. This report is the first to document toxic effects of cyclotides in plants and soil bacteria and to demonstrate that cyclotides are as toxic as commonly used herbicides and biocides. Hence, cyclotides may adversely affect soil and aquatic environments, which needs to be taken into account in future risk assessment of cropping systems for production of these highly bioactive compounds.
|
|
