Dichotomous effect of methylphenidate on microglia and astrocytes: Insights from in vitro and animal studies
Toxicol Lett. 2023 Oct 14;389:1-10. doi: 10.1016/j.toxlet.2023.10.008. Online ahead of print.ABSTRACTMethylphenidate (MPH) has been used for decades to treat attention-deficit/hyperactivity disorder (ADHD) and narcolepsy. Moreover, several studies have shown that it is subject to misuse, particularly among college students and adolescents, for cognitive enhancement or as a recreational drug. This phenomenon causes concern, and it is critical to clarify better how MPH impacts brain cells. In fact, data has suggested that MPH could result in neuroinflammation and neurodegeneration across several brain regions; however, littl...
Source: Toxicology Letters - October 16, 2023 Category: Toxicology Authors: Jo ão P Novo Mariana Muga Teresa Louren ço Eliane S Sanches Ricardo A Leit ão Ana Paula Silva Source Type: research
Dichotomous effect of methylphenidate on microglia and astrocytes: Insights from in vitro and animal studies
Toxicol Lett. 2023 Oct 14;389:1-10. doi: 10.1016/j.toxlet.2023.10.008. Online ahead of print.ABSTRACTMethylphenidate (MPH) has been used for decades to treat attention-deficit/hyperactivity disorder (ADHD) and narcolepsy. Moreover, several studies have shown that it is subject to misuse, particularly among college students and adolescents, for cognitive enhancement or as a recreational drug. This phenomenon causes concern, and it is critical to clarify better how MPH impacts brain cells. In fact, data has suggested that MPH could result in neuroinflammation and neurodegeneration across several brain regions; however, littl...
Source: Toxicology Letters - October 16, 2023 Category: Toxicology Authors: Jo ão P Novo Mariana Muga Teresa Louren ço Eliane S Sanches Ricardo A Leit ão Ana Paula Silva Source Type: research
Dichotomous effect of methylphenidate on microglia and astrocytes: Insights from in vitro and animal studies
Toxicol Lett. 2023 Oct 14:S0378-4274(23)01064-0. doi: 10.1016/j.toxlet.2023.10.008. Online ahead of print.ABSTRACTMethylphenidate (MPH) has been used for decades to treat attention-deficit/hyperactivity disorder (ADHD) and narcolepsy. Moreover, several studies have shown that it is subject to misuse, particularly among college students and adolescents, for cognitive enhancement or as a recreational drug. This phenomenon causes concern, and it is critical to clarify better how MPH impacts brain cells. In fact, data has suggested that MPH could result in neuroinflammation and neurodegeneration across several brain regions; h...
Source: Toxicology Letters - October 16, 2023 Category: Toxicology Authors: Jo ão P Novo Mariana Muga Teresa Louren ço Eliane S Sanches Ricardo A Leit ão Ana Paula Silva Source Type: research
Dichotomous effect of methylphenidate on microglia and astrocytes: Insights from in vitro and animal studies
Toxicol Lett. 2023 Oct 14:S0378-4274(23)01064-0. doi: 10.1016/j.toxlet.2023.10.008. Online ahead of print.ABSTRACTMethylphenidate (MPH) has been used for decades to treat attention-deficit/hyperactivity disorder (ADHD) and narcolepsy. Moreover, several studies have shown that it is subject to misuse, particularly among college students and adolescents, for cognitive enhancement or as a recreational drug. This phenomenon causes concern, and it is critical to clarify better how MPH impacts brain cells. In fact, data has suggested that MPH could result in neuroinflammation and neurodegeneration across several brain regions; h...
Source: Toxicology Letters - October 16, 2023 Category: Toxicology Authors: Jo ão P Novo Mariana Muga Teresa Louren ço Eliane S Sanches Ricardo A Leit ão Ana Paula Silva Source Type: research
Dichotomous effect of methylphenidate on microglia and astrocytes: Insights from in vitro and animal studies
Toxicol Lett. 2023 Oct 14:S0378-4274(23)01064-0. doi: 10.1016/j.toxlet.2023.10.008. Online ahead of print.ABSTRACTMethylphenidate (MPH) has been used for decades to treat attention-deficit/hyperactivity disorder (ADHD) and narcolepsy. Moreover, several studies have shown that it is subject to misuse, particularly among college students and adolescents, for cognitive enhancement or as a recreational drug. This phenomenon causes concern, and it is critical to clarify better how MPH impacts brain cells. In fact, data has suggested that MPH could result in neuroinflammation and neurodegeneration across several brain regions; h...
Source: Toxicology Letters - October 16, 2023 Category: Toxicology Authors: Jo ão P Novo Mariana Muga Teresa Louren ço Eliane S Sanches Ricardo A Leit ão Ana Paula Silva Source Type: research
The suitability of a polydimethylsiloxane-based (PDMS) microfluidic two compartment system for the toxicokinetic analysis of organophosphorus compounds
Toxicol Lett. 2023 Oct 10;388:24-29. doi: 10.1016/j.toxlet.2023.10.007. Online ahead of print.ABSTRACTOrgan-on-a-chip platforms are an emerging technology in experimental and regulatory toxicology (species-specific differences, ethical considerations). They address gaps between in vivo and in vitro models. However, there are still certain limitations considering material, setup and applicability. The current study examined the suitability of a commercially available polydimethylsiloxane-based (PDMS) organ-chip for the toxicokinetic characterization of the highly toxic nerve agent VX and the organophosphate pesticide parath...
Source: Toxicology Letters - October 12, 2023 Category: Toxicology Authors: Niko Amend Marianne Koller Christian Schmitt Franz Worek Timo Wille Source Type: research
The suitability of a polydimethylsiloxane-based (PDMS) microfluidic two compartment system for the toxicokinetic analysis of organophosphorus compounds
Toxicol Lett. 2023 Oct 10;388:24-29. doi: 10.1016/j.toxlet.2023.10.007. Online ahead of print.ABSTRACTOrgan-on-a-chip platforms are an emerging technology in experimental and regulatory toxicology (species-specific differences, ethical considerations). They address gaps between in vivo and in vitro models. However, there are still certain limitations considering material, setup and applicability. The current study examined the suitability of a commercially available polydimethylsiloxane-based (PDMS) organ-chip for the toxicokinetic characterization of the highly toxic nerve agent VX and the organophosphate pesticide parath...
Source: Toxicology Letters - October 12, 2023 Category: Toxicology Authors: Niko Amend Marianne Koller Christian Schmitt Franz Worek Timo Wille Source Type: research
The suitability of a polydimethylsiloxane-based (PDMS) microfluidic two compartment system for the toxicokinetic analysis of organophosphorus compounds
Toxicol Lett. 2023 Oct 10;388:24-29. doi: 10.1016/j.toxlet.2023.10.007. Online ahead of print.ABSTRACTOrgan-on-a-chip platforms are an emerging technology in experimental and regulatory toxicology (species-specific differences, ethical considerations). They address gaps between in vivo and in vitro models. However, there are still certain limitations considering material, setup and applicability. The current study examined the suitability of a commercially available polydimethylsiloxane-based (PDMS) organ-chip for the toxicokinetic characterization of the highly toxic nerve agent VX and the organophosphate pesticide parath...
Source: Toxicology Letters - October 12, 2023 Category: Toxicology Authors: Niko Amend Marianne Koller Christian Schmitt Franz Worek Timo Wille Source Type: research
The suitability of a polydimethylsiloxane-based (PDMS) microfluidic two compartment system for the toxicokinetic analysis of organophosphorus compounds
Toxicol Lett. 2023 Oct 10:S0378-4274(23)01061-5. doi: 10.1016/j.toxlet.2023.10.007. Online ahead of print.ABSTRACTOrgan-on-a-chip platforms are an emerging technology in experimental and regulatory toxicology (species-specific differences, ethical considerations). They address gaps between in vivo and in vitro models. However, there are still certain limitations considering material, setup and applicability. The current study examined the suitability of a commercially available polydimethylsiloxane-based (PDMS) organ-chip for the toxicokinetic characterization of the highly toxic nerve agent VX and the organophosphate pest...
Source: Toxicology Letters - October 12, 2023 Category: Toxicology Authors: Niko Amend Marianne Koller Christian Schmitt Franz Worek Timo Wille Source Type: research
Can a 12-gene expression signature predict the cell transforming potential of tumor promoting agents in Bhas 42 cells?
Toxicol Lett. 2023 Oct 7:S0378-4274(23)01062-7. doi: 10.1016/j.toxlet.2023.10.006. Online ahead of print.ABSTRACTTo date, long-term rodent carcinogenesis assays are the only assays recognized by regulators to assess non-genotoxic carcinogens, but their reliability has been questioned. In vitro cell transformation assays (CTAs) could represent an interesting alternative to animal models as it has the advantage of detecting both genotoxic and non-genotoxic transforming chemicals. Among them, Bhas 42 CTA uses a cell line that has been transfected with the oncogenic sequence v-Ha-ras. This sequence confers an "initiated" statu...
Source: Toxicology Letters - October 9, 2023 Category: Toxicology Authors: Yves Guichard Caroline Savoy Laurent Gat é Source Type: research
Can a 12-gene expression signature predict the cell transforming potential of tumor promoting agents in Bhas 42 cells?
Toxicol Lett. 2023 Oct 7:S0378-4274(23)01062-7. doi: 10.1016/j.toxlet.2023.10.006. Online ahead of print.ABSTRACTTo date, long-term rodent carcinogenesis assays are the only assays recognized by regulators to assess non-genotoxic carcinogens, but their reliability has been questioned. In vitro cell transformation assays (CTAs) could represent an interesting alternative to animal models as it has the advantage of detecting both genotoxic and non-genotoxic transforming chemicals. Among them, Bhas 42 CTA uses a cell line that has been transfected with the oncogenic sequence v-Ha-ras. This sequence confers an "initiated" statu...
Source: Toxicology Letters - October 9, 2023 Category: Toxicology Authors: Yves Guichard Caroline Savoy Laurent Gat é Source Type: research
Can a 12-gene expression signature predict the cell transforming potential of tumor promoting agents in Bhas 42 cells?
Toxicol Lett. 2023 Oct 7:S0378-4274(23)01062-7. doi: 10.1016/j.toxlet.2023.10.006. Online ahead of print.ABSTRACTTo date, long-term rodent carcinogenesis assays are the only assays recognized by regulators to assess non-genotoxic carcinogens, but their reliability has been questioned. In vitro cell transformation assays (CTAs) could represent an interesting alternative to animal models as it has the advantage of detecting both genotoxic and non-genotoxic transforming chemicals. Among them, Bhas 42 CTA uses a cell line that has been transfected with the oncogenic sequence v-Ha-ras. This sequence confers an "initiated" statu...
Source: Toxicology Letters - October 9, 2023 Category: Toxicology Authors: Yves Guichard Caroline Savoy Laurent Gat é Source Type: research
SGX523 causes renal toxicity through aldehyde oxidase-mediated less-soluble metabolite formation in chimeric mice with humanized livers
This study investigated the metabolism and renal toxicity of SGX523 in chimeric mice with humanized livers (humanized-liver mice). The 2-quinolinone-SGX523 formation activity was higher in humanized-liver mouse and human hepatocytes than in mouse hepatocytes. Additionally, this activity in the liver cytosolic fraction from humanized-liver mice was inhibited by the AOX inhibitors raloxifene and hydralazine. After oral SGX523 administration, higher maximum concentrations, larger areas under the plasma concentration versus time curves, and higher urinary concentrations of 2-quinolinone-SGX523 were observed in humanized-liver ...
Source: Toxicology Letters - October 8, 2023 Category: Toxicology Authors: Shotaro Uehara Masahiko Yasuda Yuichiro Higuchi Nao Yoneda Kenji Kawai Masami Suzuki Hiroshi Yamazaki Hiroshi Suemizu Source Type: research
Skin Decontamination of Carfentanil in vitro
Toxicol Lett. 2023 Oct 6:S0378-4274(23)01060-3. doi: 10.1016/j.toxlet.2023.10.005. Online ahead of print.ABSTRACTSkin decontamination of Chemical Biological Radioactive and Nuclear (CBRN) materials involves the timely and effective removal of the contaminants from the skin surface. The current work evaluated Fuller's Earth & The Reactive Skin Decontaminant Lotion Kit (RSDL®) to investigate whether they were as efficacious against free base Carfentanil skin contamination as they are against chemical warfare agents. The in vitro methodology used allowed for evaluation of decontamination regimens as specified by the deco...
Source: Toxicology Letters - October 8, 2023 Category: Toxicology Authors: Christopher Dalton Rachel Watkins Sarah Pritchard Stuart Graham Source Type: research
Predicting acute paraquat toxicity using physiologically based kinetic modelling incorporating in vitro active renal excretion via the OCT2 transporter
Toxicol Lett. 2023 Oct 6:S0378-4274(23)01058-5. doi: 10.1016/j.toxlet.2023.10.001. Online ahead of print.ABSTRACTIncluding active renal excretion in physiologically based kinetic (PBK) models can improve their use in quantitative in vitro- in vivo extrapolation (QIVIVE) as a new approach methodology (NAM) for predicting the acute toxicity of organic cation transporter 2 (OCT2) substrates like paraquat (PQ). To realise this NAM, kinetic parameters Vmax and Km for in vitro OCT2 transport of PQ were obtained from the literature. Appropriate scaling factors were applied to translate the in vitro Vmax to an in vivo Vmax. in vit...
Source: Toxicology Letters - October 8, 2023 Category: Toxicology Authors: Annelies Noorlander Sebastiaan Wesseling Ivonne M C M Rietjens Bennard van Ravenzwaay Source Type: research
