The role of hypoxia-inducible factor 1 alpha (HIF-1 α) modulation in heavy metal toxicity
Arch Toxicol. 2023 Mar 18. doi: 10.1007/s00204-023-03483-7. Online ahead of print.ABSTRACTHypoxia-inducible factor 1 (HIF-1) is an oxygen-sensing transcriptional regulator orchestrating a complex of adaptive cellular responses to hypoxia. Several studies have demonstrated that toxic metal exposure may also modulate HIF-1α signal transduction pathway, although the existing data are scarce. Therefore, the present review aims to summarize the existing data on the effects of toxic metals on HIF-1 signaling and the potential underlying mechanisms with a special focus on prooxidant effect of the metals. The particular effect of...
Source: Archives of Toxicology - March 18, 2023 Category: Toxicology Authors: Michael Aschner Anatoly V Skalny Rongzhu Lu Abel Santamaria Ji-Chang Zhou Tao Ke Mikhail Yu Karganov Aristides Tsatsakis Kirill S Golokhvast Aaron B Bowman Alexey A Tinkov Source Type: research
Dose-dependent pleiotropic role of neutrophils during acetaminophen-induced liver injury in male and female mice
Arch Toxicol. 2023 Mar 16. doi: 10.1007/s00204-023-03478-4. Online ahead of print.ABSTRACTAcetaminophen (APAP) overdose is the leading cause of acute liver failure in western countries. APAP can cause extensive hepatocellular necrosis, which triggers an inflammatory response involving neutrophil and monocyte recruitment. Particularly the role of neutrophils in the injury mechanism of APAP hepatotoxicity has been highly controversial. Thus, the objective of the current study was to assess whether a potential contribution of neutrophils was dependent on the APAP dose and the sex of the animals. Male and female C57BL/6 J mice...
Source: Archives of Toxicology - March 17, 2023 Category: Toxicology Authors: Nga T Nguyen David S Umbaugh Sawyer Smith Olamide B Adelusi Giselle Sanchez-Guerrero Anup Ramachandran Hartmut Jaeschke Source Type: research
Potency ranking of pyrrolizidine alkaloids in metabolically competent human liver cancer cells and primary human hepatocytes using a genotoxicity test battery
In conclusion, our findings strongly support the concept of grouping PAs into potency classes and help to pave the way for a broader acceptance of relative potency factors in risk assessment.PMID:36928417 | DOI:10.1007/s00204-023-03482-8 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 17, 2023 Category: Toxicology Authors: Manuel Haas Karina Wirachowski Lea Thibol Jan-Heiner K üpper Dieter Schrenk J örg Fahrer Source Type: research
Dose-dependent pleiotropic role of neutrophils during acetaminophen-induced liver injury in male and female mice
Arch Toxicol. 2023 Mar 16. doi: 10.1007/s00204-023-03478-4. Online ahead of print.ABSTRACTAcetaminophen (APAP) overdose is the leading cause of acute liver failure in western countries. APAP can cause extensive hepatocellular necrosis, which triggers an inflammatory response involving neutrophil and monocyte recruitment. Particularly the role of neutrophils in the injury mechanism of APAP hepatotoxicity has been highly controversial. Thus, the objective of the current study was to assess whether a potential contribution of neutrophils was dependent on the APAP dose and the sex of the animals. Male and female C57BL/6 J mice...
Source: Archives of Toxicology - March 17, 2023 Category: Toxicology Authors: Nga T Nguyen David S Umbaugh Sawyer Smith Olamide B Adelusi Giselle Sanchez-Guerrero Anup Ramachandran Hartmut Jaeschke Source Type: research
Potency ranking of pyrrolizidine alkaloids in metabolically competent human liver cancer cells and primary human hepatocytes using a genotoxicity test battery
In conclusion, our findings strongly support the concept of grouping PAs into potency classes and help to pave the way for a broader acceptance of relative potency factors in risk assessment.PMID:36928417 | DOI:10.1007/s00204-023-03482-8 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 17, 2023 Category: Toxicology Authors: Manuel Haas Karina Wirachowski Lea Thibol Jan-Heiner K üpper Dieter Schrenk J örg Fahrer Source Type: research
Organoid-based 3D in vitro microphysiological systems as alternatives to animal experimentation for preclinical and clinical research
Arch Toxicol. 2023 Mar 14. doi: 10.1007/s00204-023-03466-8. Online ahead of print.NO ABSTRACTPMID:36917352 | DOI:10.1007/s00204-023-03466-8 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 14, 2023 Category: Toxicology Authors: Chrianjay Mukhopadhyay Manash K Paul Source Type: research
In memoriam Thomas Gebel
Arch Toxicol. 2023 Mar 14. doi: 10.1007/s00204-023-03473-9. Online ahead of print.NO ABSTRACTPMID:36917353 | DOI:10.1007/s00204-023-03473-9 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 14, 2023 Category: Toxicology Authors: Jan G Hengstler Hermann Bolt Uwe Heinrich Andrea Hartwig Robert Landsiedel Source Type: research
Organoid-based 3D in vitro microphysiological systems as alternatives to animal experimentation for preclinical and clinical research
Arch Toxicol. 2023 Mar 14. doi: 10.1007/s00204-023-03466-8. Online ahead of print.NO ABSTRACTPMID:36917352 | DOI:10.1007/s00204-023-03466-8 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 14, 2023 Category: Toxicology Authors: Chrianjay Mukhopadhyay Manash K Paul Source Type: research
In memoriam Thomas Gebel
Arch Toxicol. 2023 Mar 14. doi: 10.1007/s00204-023-03473-9. Online ahead of print.NO ABSTRACTPMID:36917353 | DOI:10.1007/s00204-023-03473-9 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 14, 2023 Category: Toxicology Authors: Jan G Hengstler Hermann Bolt Uwe Heinrich Andrea Hartwig Robert Landsiedel Source Type: research
Organoid-based 3D in vitro microphysiological systems as alternatives to animal experimentation for preclinical and clinical research
Arch Toxicol. 2023 Mar 14. doi: 10.1007/s00204-023-03466-8. Online ahead of print.NO ABSTRACTPMID:36917352 | DOI:10.1007/s00204-023-03466-8 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 14, 2023 Category: Toxicology Authors: Chrianjay Mukhopadhyay Manash K Paul Source Type: research
In memoriam Thomas Gebel
Arch Toxicol. 2023 Mar 14. doi: 10.1007/s00204-023-03473-9. Online ahead of print.NO ABSTRACTPMID:36917353 | DOI:10.1007/s00204-023-03473-9 (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 14, 2023 Category: Toxicology Authors: Jan G Hengstler Hermann Bolt Uwe Heinrich Andrea Hartwig Robert Landsiedel Source Type: research
Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) causes seizure activity in larval zebrafish via antagonism of γ-aminobutyric acid type A receptor α1β2γ2
Arch Toxicol. 2023 Mar 13. doi: 10.1007/s00204-023-03475-7. Online ahead of print.ABSTRACTHexahydro-1,3,5-trinitro-1,3,5-triazine, or Royal Demolition Explosive (RDX), is a major component of plastic explosives such as C-4. Acute exposures from intentional or accidental ingestion are a documented clinical concern, especially among young male U.S. service members in the armed forces. When ingested in large enough quantity, RDX causes tonic-clonic seizures. Previous in silico and in vitro experiments predict that RDX causes seizures by inhibiting α1β2γ2 γ-aminobutyric acid type A (GABAA) receptor-mediated chloride curren...
Source: Archives of Toxicology - March 13, 2023 Category: Toxicology Authors: Paige C Mundy Alicia Werner Latika Singh Vikrant Singh Rosalia Mendieta Caitlyn E Patullo Heike Wulff Pamela J Lein Source Type: research
PBTK modeling of the pyrrolizidine alkaloid retrorsine to predict liver toxicity in mouse and rat
Arch Toxicol. 2023 Mar 11. doi: 10.1007/s00204-023-03453-z. Online ahead of print.ABSTRACTRetrorsine is a hepatotoxic pyrrolizidine alkaloid (PA) found in herbal supplements and medicines, food and livestock feed. Dose-response studies enabling the derivation of a point of departure including a benchmark dose for risk assessment of retrorsine in humans and animals are not available. Addressing this need, a physiologically based toxicokinetic (PBTK) model of retrorsine was developed for mouse and rat. Comprehensive characterization of retrorsine toxicokinetics revealed: both the fraction absorbed from the intestine (78%) an...
Source: Archives of Toxicology - March 11, 2023 Category: Toxicology Authors: Anja Lehmann Ina Geburek Anja These Stefanie Hessel-Pras Jan G Hengstler Wiebke Albrecht Hans Mielke Christine M üller-Graf Xiaojing Yang Charlotte Kloft Christoph Hethey Source Type: research
PBTK modeling of the pyrrolizidine alkaloid retrorsine to predict liver toxicity in mouse and rat
Arch Toxicol. 2023 Mar 11. doi: 10.1007/s00204-023-03453-z. Online ahead of print.ABSTRACTRetrorsine is a hepatotoxic pyrrolizidine alkaloid (PA) found in herbal supplements and medicines, food and livestock feed. Dose-response studies enabling the derivation of a point of departure including a benchmark dose for risk assessment of retrorsine in humans and animals are not available. Addressing this need, a physiologically based toxicokinetic (PBTK) model of retrorsine was developed for mouse and rat. Comprehensive characterization of retrorsine toxicokinetics revealed: both the fraction absorbed from the intestine (78%) an...
Source: Archives of Toxicology - March 11, 2023 Category: Toxicology Authors: Anja Lehmann Ina Geburek Anja These Stefanie Hessel-Pras Jan G Hengstler Wiebke Albrecht Hans Mielke Christine M üller-Graf Xiaojing Yang Charlotte Kloft Christoph Hethey Source Type: research
PBTK modeling of the pyrrolizidine alkaloid retrorsine to predict liver toxicity in mouse and rat
Arch Toxicol. 2023 Mar 11. doi: 10.1007/s00204-023-03453-z. Online ahead of print.ABSTRACTRetrorsine is a hepatotoxic pyrrolizidine alkaloid (PA) found in herbal supplements and medicines, food and livestock feed. Dose-response studies enabling the derivation of a point of departure including a benchmark dose for risk assessment of retrorsine in humans and animals are not available. Addressing this need, a physiologically based toxicokinetic (PBTK) model of retrorsine was developed for mouse and rat. Comprehensive characterization of retrorsine toxicokinetics revealed: both the fraction absorbed from the intestine (78%) an...
Source: Archives of Toxicology - March 11, 2023 Category: Toxicology Authors: Anja Lehmann Ina Geburek Anja These Stefanie Hessel-Pras Jan G Hengstler Wiebke Albrecht Hans Mielke Christine M üller-Graf Xiaojing Yang Charlotte Kloft Christoph Hethey Source Type: research
