Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA392304 | ENA |
REPOSITORIES: ENA
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Project description:Overdose of acetaminophen (APAP) is the major cause of acute liver failure in the Western world with very limited treatment options. Previous studies from our groups and others have shown that timely activation of liver regeneration is a critical determinant of transplant-free survival of APAP-induced acute liver failure (ALF) patients. We used affy microarrays to explore the mechanisms of transcriptional expression in YAP-KO mice after 300mg/kg APAP overdose.
2021-10-04 | GSE183119 | GEO
Project description:Acetaminophen (APAP) overdose can lead to acute kidney injury (AKI), yet its molecular mechanisms remain unclear and no effective treatments are currently available. In this study, we combined transcriptomic, proteomic, and phosphoproteomic profiling of kidneys from APAP-exposed mice to explore molecular mechanisms and potential therapeutic strategies. Ten-week-old male C57BL/6 mice were fasted overnight for 16 hours prior to APAP treatment. Acute kidney injury was induced by intraperitoneal injection of APAP overdose (300 mg/kg body weight) for 6 hours (n = 4). Control mice received an equivalent volume of PBS via intraperitoneal injection (n = 4). Kidney tissues were subsequently collected from APAP-induced kidney injury mice and PBS-injected controls.
2025-12-05 | PXD063126 | Pride
Project description:Acetaminophen (APAP) is the most widely used analgesic in the United States. Its acute overdose causes liver damage by inducing localized centrilobular cell death. Because of widespread use, APAP toxicity has become the most frequent cause of acute liver failure. Many factors have been associated with the susceptibility of APAP-induced liver injuries, however, few of them have been confirmed and used in the clinical setting. We tried to identify the subset of factors that could affect susceptibility to APAP-induced liver injury by an integrative genetic, transcriptional and 2-D-NMR-based metabolomic analysis across a panel of inbred mouse strains. Experiment Overall Design: After a single administration of high dose (300 mg/kg i.p.) APAP, liver and blood samples were extracted from 3 sensitive (C57B6, DBA/2, and SmJ) and 1 resistant (SJL) mice strains at 0, 3 and 6 hour after APAP exposure. Endogenous metabolites from liver samples were analyzed by 1H-13C 2-dimensional-NMR and gene expression changes occurring within these liver samples were simultaneously analyzed using Affymetrix microarrays. The transcriptional and metabolomic data was jointly analyzed, and functional information within the Gene Ontology database was used to identify the subset of genes that could affect susceptibility to APAP-induced liver injury in the early phase response.
2009-08-23 | E-GEOD-17649 | biostudies-arrayexpress
Project description:Acetaminophen (APAP) overdose can cause acute kidney injury (AKI), but its molecular mechanisms remain poorly understood and no effective treatments are currently available. In this study, we performed an integrated analysis combining transcriptomic, proteomic, and phosphoproteomic profiling of kidney tissues from APAP-treated mice to investigate the underlying molecular mechanisms and identify potential therapeutic targets. Ten-week-old male C57BL/6 mice were fasted overnight for 16 hours prior to APAP administration. AKI was induced by intraperitoneal injection of a high dose of APAP (300 mg/kg body weight) for 6 hours (n = 4), while control mice received an equivalent volume of PBS via intraperitoneal injection (n = 4). Kidney tissues were collected from both APAP-treated and control groups for downstream omics analyses.
2025-11-24 | PXD063122 | Pride
Project description:Fifty percent of all acute liver failure (ALF) cases in the United States are due to acetaminophen (APAP) overdose. Assessment of canonical features of liver injury, such as plasma alanine aminotransferase activities are poor predictors of acute liver failure (ALF), suggesting the involvement of additional mechanisms independent of hepatocyte death. Previous work demonstrated a severe overdose of APAP results in impaired regeneration, the induction of senescence by p21, and increased mortality. We hypothesized that a discrete population of p21+ hepatocytes acquired a secretory phenotype that directly impedes liver recovery after a severe APAP overdose. Leveraging in-house human APAP explant liver and publicly available singlenuclei RNAseq data, we identified a subpopulation of p21+ hepatocytes enriched in a unique secretome of factors, such as Cxcl14. Spatial transcriptomics in the mouse model of APAP overdose confirmed the presence of a p21+ hepatocyte population that directly surrounded the necrotic areas. In both male and female mice, we found a dose-dependent induction of p21 and persistent circulating levels of the p21-specific constituent, Cxcl14, in the plasma after a severe APAP overdose. In parallel experiments, we targeted either the putative senescent hepatocytes with the senolytic drugs, dasatinib and quercetin, or Cxcl14 with a neutralizing antibody. We found that targeting Cxcl14 greatly enhanced liver recovery after APAP-induced liver injury, while targeting the senescent hepatocyte had no effect. This data supports that the sustained induction of p21 in hepatocytes with persistent Cxcl14 secretion are critical mechanistic events leading to ALF in mice and human patients.
2024-04-15 | GSE255834 | GEO
Project description:Fifty percent of all acute liver failure (ALF) cases in the United States are due to acetaminophen (APAP) overdose. Assessment of canonical features of liver injury, such as plasma alanine aminotransferase activities are poor predictors of acute liver failure (ALF), suggesting the involvement of additional mechanisms independent of hepatocyte death. Previous work demonstrated a severe overdose of APAP results in impaired regeneration, the induction of senescence by p21, and increased mortality. We hypothesized that a discrete population of p21+ hepatocytes acquired a secretory phenotype that directly impedes liver recovery after a severe APAP overdose. Leveraging in-house human APAP explant liver and publicly available singlenuclei RNAseq data, we identified a subpopulation of p21+ hepatocytes enriched in a unique secretome of factors, such as Cxcl14. Spatial transcriptomics in the mouse model of APAP overdose confirmed the presence of a p21+ hepatocyte population that directly surrounded the necrotic areas. In both male and female mice, we found a dose-dependent induction of p21 and persistent circulating levels of the p21-specific constituent, Cxcl14, in the plasma after a severe APAP overdose. In parallel experiments, we targeted either the putative senescent hepatocytes with the senolytic drugs, dasatinib and quercetin, or Cxcl14 with a neutralizing antibody. We found that targeting Cxcl14 greatly enhanced liver recovery after APAP-induced liver injury, while targeting the senescent hepatocyte had no effect. This data supports that the sustained induction of p21 in hepatocytes with persistent Cxcl14 secretion are critical mechanistic events leading to ALF in mice and human patients.
2024-04-15 | GSE255777 | GEO
Project description:To study the global changes of liver transcriptome after acetaminophen overdose. To study the global changes of transcriptome in the liver after acetaminophen overdose. Eight week old female C57BL/6 mice were fasted for 24 hours prior to a single intraperitoneal injection of 350mg/kg of acetaminophen in phosphate buffer saline (PBS) (treatment group) or PBS (control group). The mice were euthanized at different time points post exposure; plasma and tissue samples were collected for pathological examination and biochemical analyses.
2013-05-03 | E-GEOD-42181 | biostudies-arrayexpress
Project description:To study the global changes of liver transcriptome after acetaminophen overdose. To study the global changes of transcriptome in the liver after acetaminophen overdose. Eight week old female C57BL/6 mice were fasted for 24 hours prior to a single intraperitoneal injection of 350mg/kg of acetaminophen in phosphate buffer saline (PBS) (treatment group) or PBS (control group). The mice were euthanized at different time points post exposure; plasma and tissue samples were collected for pathological examination and biochemical analyses.
2013-05-03 | E-GEOD-42178 | biostudies-arrayexpress
Project description:Genetic disruption of thioredoxin reductase 1 protects against acetaminophen (APAP) toxicity. To determine the role of the thioredoxin system on xenobiotic metabolism we challeneged wildtype and txnrd1liver-null mice with acetaminophen. Adult male wildtype and txnrd1 liver-null mice (C57BL6/J) were treated with either saline (PBS) or 100mg/kg APAP. Liver RNA was harvested eight hours after challenge and processed for microarray analysis. Comparison of 2 treatment conditions in 2 genotypes, biological replicates in triplicate.
2013-06-08 | E-GEOD-37874 | biostudies-arrayexpress
Project description:Acetaminophen (APAP) overdose is a known cause of acute kidney injury, yet the underlying molecular mechanisms remain incompletely understood. In this study, we conducted integrated transcriptomic, proteomic, and phosphoproteomic analyses of kidney tissues from mice with early-stage APAP-induced nephrotoxicity and corresponding controls.
2025-12-04 | GSE295115 | GEO