A5058658999- Toxic Organic Pollutants Impact
- Pharmacogenetics and Drug Metabolism
- Environmental Toxicology and Ecotoxicology
- Effects and risks of endocrine disrupting chemicals
- Per- and polyfluoroalkyl substances research
- Zebrafish Biomedical Research Applications
- Receptor Mechanisms and Signaling
- Air Quality and Health Impacts
- Epigenetics and DNA Methylation
- Carcinogens and Genotoxicity Assessment
- Genomics, phytochemicals, and oxidative stress
- Vitamin D Research Studies
- Dermatology and Skin Diseases
- Synthesis of Indole Derivatives
- Estrogen and related hormone effects
- Synthesis and biological activity
- Immunotoxicology and immune responses
- Adenosine and Purinergic Signaling
- Psoriasis: Treatment and Pathogenesis
- Synthesis and Biological Evaluation
- Chemical Safety and Risk Management
- Chemical Reactions and Isotopes
- Immune Response and Inflammation
- Histone Deacetylase Inhibitors Research
- Quantum Electrodynamics and Casimir Effect
Karolinska Institutet
2016-2025
Woods Hole Oceanographic Institution
2016
Uppsala University
2015
Stockholm University
2004-2012
Dioxins and other polycyclic aromatic compounds formed during the combustion of waste fossil fuels represent a risk to human health, as well being our environment. Compounds this nature exert carcinogenic endocrine-disrupting effects in experimental animals by binding orphan aryl hydrocarbon receptor (AhR). Understanding mechanism action these pollutants, physiological role(s) AhR, requires identification endogenous ligand(s) receptor. We reported earlier that activation AhR ultraviolet...
Altered systemic levels of 6-formylindolo[3,2-b]carbazole (FICZ), an enigmatic endogenous ligand for the aryl hydrocarbon receptor (AHR), may explain adverse physiological responses evoked by small natural and anthropogenic molecules as well oxidative stress light. We demonstrate here that several different chemical compounds can inhibit metabolism FICZ, thereby disrupting autoregulatory feedback control cytochrome P4501 systems other proteins whose expression is regulated AHR. FICZ both...
Several polyphenols have been shown to activate the aryl hydrocarbon receptor (AHR) in spite of fact that they bind with low affinity. The aim this study was investigate whether quercetin (QUE), resveratrol (RES), and curcumin (CUR) interfere metabolic degradation suggested endogenous AHR ligand 6-formylindolo[3,2-b]carbazole (FICZ) thereby indirectly AHR. Using recombinant human enzyme, we confirmed earlier reported inhibitory effects on cytochrome P4501A1 (CYP1A1) activity, inhibition...
Activation of the aryl hydrocarbon receptor (AhR), a conserved transcription factor best known as target for highly toxic halogenated substances such dioxin, under normal xenobiotic-free conditions is considerable scientific interest. We have demonstrated previously that photoproduct tryptophan, 6-formylindolo[3,2-b]carbazole (FICZ), fulfills criteria an endogenous ligand this and proposed compound enigmatic mediator physiological functions AhR. Here, we describe novel light-independent...
Many industrial sites are polluted by complex mixtures of polycyclic aromatic compounds (PACs). Besides hydrocarbons (PAHs), these often contain significant amounts more polar PACs including oxygenated PAHs (oxy-PAHs). The effects oxy-PAHs are, however, poorly known. Here we used zebrafish embryos to examine toxicities and transcriptional changes induced PAC containing soil extracts from three different sites: a gasworks (GAS), former wood preservation site (WOOD), coke oven (COKE), PAH...
Perfluorinated alkyl acids (PFAA) are highly persistent and bioaccumulative have been associated with several adverse health effects. The chemical structure mainly differs in two ways: the length of hydrophobic chain type hydrophilic end group. Little is known how affects toxicokinetics (TK) different organisms. We studied TK four PFAA (PFOS, PFHxS, PFOA, PFBA) lengths (4–8 carbons) functional groups (sulfonic carboxylic acid) zebrafish (Danio rerio) embryo. time courses external (ambient...
Many chemicals accumulate in organisms through a variety of different mechanisms. Cationic amphiphilic drugs (CADs) lysosomes and bind to membranes causing phospholipidosis, whereas many lipophilic target adipose tissue. Perfluoroalkyl substances (PFASs) are widely used as surfactants, but them highly bioaccumulating persistent the environment, making notorious environmental toxicants. Understanding mechanisms their bioaccumulation is, therefore, important for regulation substitution with...
6-Formylindolo[3,2-b]carbazole (FICZ) is a potent aryl hydrocarbon receptor (AHR) agonist that efficiently metabolized by AHR-regulated cytochrome P4501 enzymes. FICZ proposed physiological AHR ligand induces its own degradation as part of regulatory negative feedback loop. In vitro studies in cells show CYP1 inhibition the presence results enhanced activation, suggesting accumulates cell when metabolism blocked. We used zebrafish (Danio rerio) embryos to investigate vivo effects CYP1A...
Our data represent the first demonstration that oxy-PAHs can be potent inhibitors of CYP1 expression and function.
The aryl hydrocarbon receptor (AHR) controls interleukin 22 production by T helper 17 cells (Th17). IL-22 contributes to intestinal homeostasis but has also been implicated in chronic inflammatory disorders and colorectal cancer, highlighting the need for appropriate regulation of production. Upon activation, AHR induces expression cytochrome P4501 (CYP1) enzymes which turn play an important feedback role that curtails duration signaling metabolizing ligands. Recently we described how agents...
The intestinal epithelium is continuously exposed to deleterious environmental factors that might cause aberrant immune responses leading inflammatory disorders. However, what contribute disease are poorly understood. Here, overcome the lack of in vivo models suitable for screening factors, we used zebrafish reporters inflammation. Using zebrafish, interrogated immunomodulatory effects polyfluoroalkyl substances, which have been positively associated with ulcerative colitis incidence....
Polycyclic aromatic hydrocarbons (PAHs) are widely spread environmental contaminants which affect developing organisms. It is known that improper activation of the aryl hydrocarbon receptor (AhR) by some PAHs contributes to toxicity, while other can disrupt cellular membrane function. The exact downstream mechanisms AhR remain unresolved, especially with regard cardiotoxicity. By exposing newly hatched rainbow trout alevins (Oncorhynchus mykiss) semi-statically retene (32 µg l-1; agonist),...
Polycyclic aromatic hydrocarbons (PAHs) and pesticides are two major groups of environmental contaminants which humans simultaneously exposed to. However, potential mixture interactions these chemicals not well-studied. In this study, the effects binary mixtures PAH benzo[a]pyrene (B[a]P) commonly used chlorpyrifos, paraquat tebuconazole on human liver HepG2 cells were investigated. The results showed that B[a]P or mainly caused additive cell viability cytochrome P4501a1 (CYP1A1) expression...
Manuka honey (MH) is a complex nutritional material with antimicrobial, antioxidant and anti-inflammatory activity. We have previously shown that MH down regulates IL-4-induced CCL26 expression in immortalized keratinocytes. As contains potential ligands of the Aryl Hydrocarbon Receptor (AHR), key regulator skin homeostasis, we hypothesize this effect mediated via AHR activation. Here, treated HaCaT cell lines, either stable transfected an empty vector (EV-HaCaT) or which had been silenced...
Persistent and semi-persistent halogenated compounds cause health problems for the animals occupying upper level of food web in Baltic Sea. Atlantic salmon (Salmo salar), being a top piscivore Sea, has been observed to carry large body burden toxins. Here, mixture nine belonging different groups was created, based on composition toxins serum. The toxicokinetic properties were studied zebrafish (Danio rerio) embryos achieve same proportions between internal doses as salmon. Toxicity evaluated...