Screening for endocrine disrupting chemicals inhibiting monocarboxylate 8 (MCT8) transporter facilitated thyroid hormone transport using a modified nonradioactive assay
This study explored the use of an UV-light digestion step as an alternative for the original ammonium persulfate (APS) digestion step. The non-radioactive TH uptake assay, with the incorporated UV-light digestion step of TH, was then used to screen a set of 32 reference chemicals and environmentally relevant substances to detect inhibition of MCT8-depending T3 uptake. This alternative assay identified three novel MCT8 inhibitors: methylmercury, bisphenol-AF and bisphenol-Z and confirmed previously known MCT8 inhibitors.PMID:38151217 | DOI:10.1016/j.tiv.2023.105770 (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - December 27, 2023 Category: Toxicology Authors: Fabian Wagenaars Peter Cenijn Martin Scholze Caroline Fr ädrich Kostja Renko Josef K öhrle Timo Hamers Source Type: research

Screening for endocrine disrupting chemicals inhibiting monocarboxylate 8 (MCT8) transporter facilitated thyroid hormone transport using a modified nonradioactive assay
This study explored the use of an UV-light digestion step as an alternative for the original ammonium persulfate (APS) digestion step. The non-radioactive TH uptake assay, with the incorporated UV-light digestion step of TH, was then used to screen a set of 32 reference chemicals and environmentally relevant substances to detect inhibition of MCT8-depending T3 uptake. This alternative assay identified three novel MCT8 inhibitors: methylmercury, bisphenol-AF and bisphenol-Z and confirmed previously known MCT8 inhibitors.PMID:38151217 | DOI:10.1016/j.tiv.2023.105770 (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - December 27, 2023 Category: Toxicology Authors: Fabian Wagenaars Peter Cenijn Martin Scholze Caroline Fr ädrich Kostja Renko Josef K öhrle Timo Hamers Source Type: research

Screening for endocrine disrupting chemicals inhibiting monocarboxylate 8 (MCT8) transporter facilitated thyroid hormone transport using a modified nonradioactive assay
This study explored the use of an UV-light digestion step as an alternative for the original ammonium persulfate (APS) digestion step. The non-radioactive TH uptake assay, with the incorporated UV-light digestion step of TH, was then used to screen a set of 32 reference chemicals and environmentally relevant substances to detect inhibition of MCT8-depending T3 uptake. This alternative assay identified three novel MCT8 inhibitors: methylmercury, bisphenol-AF and bisphenol-Z and confirmed previously known MCT8 inhibitors.PMID:38151217 | DOI:10.1016/j.tiv.2023.105770 (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - December 27, 2023 Category: Toxicology Authors: Fabian Wagenaars Peter Cenijn Martin Scholze Caroline Fr ädrich Kostja Renko Josef K öhrle Timo Hamers Source Type: research

Screening for endocrine disrupting chemicals inhibiting monocarboxylate 8 (MCT8) transporter facilitated thyroid hormone transport using a modified nonradioactive assay
This study explored the use of an UV-light digestion step as an alternative for the original ammonium persulfate (APS) digestion step. The non-radioactive TH uptake assay, with the incorporated UV-light digestion step of TH, was then used to screen a set of 32 reference chemicals and environmentally relevant substances to detect inhibition of MCT8-depending T3 uptake. This alternative assay identified three novel MCT8 inhibitors: methylmercury, bisphenol-AF and bisphenol-Z and confirmed previously known MCT8 inhibitors.PMID:38151217 | DOI:10.1016/j.tiv.2023.105770 (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - December 27, 2023 Category: Toxicology Authors: Fabian Wagenaars Peter Cenijn Martin Scholze Caroline Fr ädrich Kostja Renko Josef K öhrle Timo Hamers Source Type: research

Screening for endocrine disrupting chemicals inhibiting monocarboxylate 8 (MCT8) transporter facilitated thyroid hormone transport using a modified nonradioactive assay
This study explored the use of an UV-light digestion step as an alternative for the original ammonium persulfate (APS) digestion step. The non-radioactive TH uptake assay, with the incorporated UV-light digestion step of TH, was then used to screen a set of 32 reference chemicals and environmentally relevant substances to detect inhibition of MCT8-depending T3 uptake. This alternative assay identified three novel MCT8 inhibitors: methylmercury, bisphenol-AF and bisphenol-Z and confirmed previously known MCT8 inhibitors.PMID:38151217 | DOI:10.1016/j.tiv.2023.105770 (Source: Toxicology in Vitro)
Source: Toxicology in Vitro - December 27, 2023 Category: Toxicology Authors: Fabian Wagenaars Peter Cenijn Martin Scholze Caroline Fr ädrich Kostja Renko Josef K öhrle Timo Hamers Source Type: research

Comparison of in vitro thyroxine (T4) metabolism between Wistar rat and human hepatocyte cultures
Toxicol In Vitro. 2023 Dec 22:105763. doi: 10.1016/j.tiv.2023.105763. Online ahead of print.ABSTRACTIn vitro assays remain relatively new in exploring human relevance of liver-, in particular nuclear receptor-mediated perturbations of the hypothalamus-pituitary-thyroid axis seen in rodents, mainly in the rat. Consistent with in vivo data, we confirm that thyroid hormone thyroxine metabolism was 9 times higher in primary rat hepatocytes (PRH) than in primary human hepatocytes (PHH) cultured in a 2D sandwich configuration. In addition, thyroxine glucuronide (T4-G) was by far the major metabolite formed in both species (99.1%...
Source: Toxicology in Vitro - December 24, 2023 Category: Toxicology Authors: Audrey Baze Lucille Wiss Liliia Horbal Klaus Biemel Laure Asselin Lysiane Richert Source Type: research

Fragrances as a trigger of immune responses in different environments
Toxicol In Vitro. 2023 Dec 22:105769. doi: 10.1016/j.tiv.2023.105769. Online ahead of print.ABSTRACTFragrances can cause allergic skin reactions, expressed as allergic contact dermatitis and reactions in the respiratory tract that range from acute temporary upper airway irritation to obstructive lung disease. These adverse health effects may result from the stimulation of a specific (adaptive) immune response. Th1 cells, which essentially produce interleukin-2 (IL-2) and interferon-γ (IFN-γ), play a key role in allergic contact dermatitis and also on allergic sensitization to common allergens (e.g., nickel and fragrance)...
Source: Toxicology in Vitro - December 24, 2023 Category: Toxicology Authors: M Macchione K Yoshizaki D P Frias K Maier J Smelan C M Prado T Mauad Source Type: research

Comparison of in vitro thyroxine (T4) metabolism between Wistar rat and human hepatocyte cultures
Toxicol In Vitro. 2023 Dec 22:105763. doi: 10.1016/j.tiv.2023.105763. Online ahead of print.ABSTRACTIn vitro assays remain relatively new in exploring human relevance of liver-, in particular nuclear receptor-mediated perturbations of the hypothalamus-pituitary-thyroid axis seen in rodents, mainly in the rat. Consistent with in vivo data, we confirm that thyroid hormone thyroxine metabolism was 9 times higher in primary rat hepatocytes (PRH) than in primary human hepatocytes (PHH) cultured in a 2D sandwich configuration. In addition, thyroxine glucuronide (T4-G) was by far the major metabolite formed in both species (99.1%...
Source: Toxicology in Vitro - December 24, 2023 Category: Toxicology Authors: Audrey Baze Lucille Wiss Liliia Horbal Klaus Biemel Laure Asselin Lysiane Richert Source Type: research

Fragrances as a trigger of immune responses in different environments
Toxicol In Vitro. 2023 Dec 22:105769. doi: 10.1016/j.tiv.2023.105769. Online ahead of print.ABSTRACTFragrances can cause allergic skin reactions, expressed as allergic contact dermatitis and reactions in the respiratory tract that range from acute temporary upper airway irritation to obstructive lung disease. These adverse health effects may result from the stimulation of a specific (adaptive) immune response. Th1 cells, which essentially produce interleukin-2 (IL-2) and interferon-γ (IFN-γ), play a key role in allergic contact dermatitis and also on allergic sensitization to common allergens (e.g., nickel and fragrance)...
Source: Toxicology in Vitro - December 24, 2023 Category: Toxicology Authors: M Macchione K Yoshizaki D P Frias K Maier J Smelan C M Prado T Mauad Source Type: research

Comparison of in vitro thyroxine (T4) metabolism between Wistar rat and human hepatocyte cultures
Toxicol In Vitro. 2023 Dec 22:105763. doi: 10.1016/j.tiv.2023.105763. Online ahead of print.ABSTRACTIn vitro assays remain relatively new in exploring human relevance of liver-, in particular nuclear receptor-mediated perturbations of the hypothalamus-pituitary-thyroid axis seen in rodents, mainly in the rat. Consistent with in vivo data, we confirm that thyroid hormone thyroxine metabolism was 9 times higher in primary rat hepatocytes (PRH) than in primary human hepatocytes (PHH) cultured in a 2D sandwich configuration. In addition, thyroxine glucuronide (T4-G) was by far the major metabolite formed in both species (99.1%...
Source: Toxicology in Vitro - December 24, 2023 Category: Toxicology Authors: Audrey Baze Lucille Wiss Liliia Horbal Klaus Biemel Laure Asselin Lysiane Richert Source Type: research

Fragrances as a trigger of immune responses in different environments
Toxicol In Vitro. 2023 Dec 22:105769. doi: 10.1016/j.tiv.2023.105769. Online ahead of print.ABSTRACTFragrances can cause allergic skin reactions, expressed as allergic contact dermatitis and reactions in the respiratory tract that range from acute temporary upper airway irritation to obstructive lung disease. These adverse health effects may result from the stimulation of a specific (adaptive) immune response. Th1 cells, which essentially produce interleukin-2 (IL-2) and interferon-γ (IFN-γ), play a key role in allergic contact dermatitis and also on allergic sensitization to common allergens (e.g., nickel and fragrance)...
Source: Toxicology in Vitro - December 24, 2023 Category: Toxicology Authors: M Macchione K Yoshizaki D P Frias K Maier J Smelan C M Prado T Mauad Source Type: research

Dinaciclib inhibits the growth of acute myeloid leukemia cells through either cell cycle-related or ERK1/STAT3/MYC pathways
Toxicol In Vitro. 2023 Dec 20:105768. doi: 10.1016/j.tiv.2023.105768. Online ahead of print.ABSTRACTAlthough immature differentiation and uncontrolled proliferation of hematopoietic stem cells are thought to be the primary mechanisms of acute myeloid leukemia (AML), the pathophysiology in most cases remains unclear. Dinaciclib, a selective small molecule targeting multiple cyclin-dependent kinases (CDKs), is currently being evaluated in oncological clinical trials. Despite the proven anticancer potential of dinaciclib, the differential molecular mechanisms by which it inhibits the growth of different AML cell lines remain ...
Source: Toxicology in Vitro - December 22, 2023 Category: Toxicology Authors: Chieh-Lin Jerry Teng Pang-Ting Cheng Yu-Chiao Cheng Jia-Rung Tsai Mei-Chih Chen Ho Lin Source Type: research

Dinaciclib inhibits the growth of acute myeloid leukemia cells through either cell cycle-related or ERK1/STAT3/MYC pathways
Toxicol In Vitro. 2023 Dec 20:105768. doi: 10.1016/j.tiv.2023.105768. Online ahead of print.ABSTRACTAlthough immature differentiation and uncontrolled proliferation of hematopoietic stem cells are thought to be the primary mechanisms of acute myeloid leukemia (AML), the pathophysiology in most cases remains unclear. Dinaciclib, a selective small molecule targeting multiple cyclin-dependent kinases (CDKs), is currently being evaluated in oncological clinical trials. Despite the proven anticancer potential of dinaciclib, the differential molecular mechanisms by which it inhibits the growth of different AML cell lines remain ...
Source: Toxicology in Vitro - December 22, 2023 Category: Toxicology Authors: Chieh-Lin Jerry Teng Pang-Ting Cheng Yu-Chiao Cheng Jia-Rung Tsai Mei-Chih Chen Ho Lin Source Type: research

Delayed clearance of the pro-carcinogen benzo[a]pyrene in PLHC-1 cells when co-exposed to the antifungal drug clotrimazole and effects on the CYP1A biomarker
Toxicol In Vitro. 2023 Dec 18:105767. doi: 10.1016/j.tiv.2023.105767. Online ahead of print.ABSTRACTCytochrome P450 1 A (CYP1A) is a key enzyme in the metabolism of the polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BaP) in animals, and a biomarker for environmental PAH exposure. The common antimycotic imidazole drug clotrimazole (CLO) has been detected in the aquatic environment and likely co-exists with BaP. Like BaP, CLO can bind to CYP1A enzymes and can act as a CYP1A inhibitor. Co-exposure of BaP with CLO significantly delayed BaP elimination in a fish liver cell line (PLHC-1). Intracellular BaP concentration w...
Source: Toxicology in Vitro - December 20, 2023 Category: Toxicology Authors: Maja Edenius Anne Farbrot Anders Blom Malin C Celander Source Type: research

Delayed clearance of the pro-carcinogen benzo[a]pyrene in PLHC-1 cells when co-exposed to the antifungal drug clotrimazole and effects on the CYP1A biomarker
Toxicol In Vitro. 2023 Dec 18:105767. doi: 10.1016/j.tiv.2023.105767. Online ahead of print.ABSTRACTCytochrome P450 1 A (CYP1A) is a key enzyme in the metabolism of the polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BaP) in animals, and a biomarker for environmental PAH exposure. The common antimycotic imidazole drug clotrimazole (CLO) has been detected in the aquatic environment and likely co-exists with BaP. Like BaP, CLO can bind to CYP1A enzymes and can act as a CYP1A inhibitor. Co-exposure of BaP with CLO significantly delayed BaP elimination in a fish liver cell line (PLHC-1). Intracellular BaP concentration w...
Source: Toxicology in Vitro - December 20, 2023 Category: Toxicology Authors: Maja Edenius Anne Farbrot Anders Blom Malin C Celander Source Type: research