Drug-Induced Hepatotoxicity and Protection

Towards Bayesian-based quantitative adverse outcome pathways using in vitro data from open literature and continuous variables: a case example for liver fibrosis.

This paper develops a Bayesian-based model using in vitro data and continuous variables to predict liver fibrosis by analyzing key markers of hepatic stellate cell activation.

Cell line identity rather than medium composition determines transcriptomic profiles of HepaRG and HuH7 cells cultured in chemically defined or serum-based media: comparison with primary human hepatocytes

This study compares transcriptomic profiles of HepaRG and HuH7 cells cultured in chemically defined or serum-based media, finding that cell line identity, not medium composition, is the main determinant of transcriptomic variance.

Sublethal stress from polypharmacy modulates scavenging function and fenestrations in mouse liver sinusoidal endothelial cells

This study examines how polypharmacy affects liver sinusoidal endothelial cells, showing drug- and concentration-dependent changes in fenestrations and endocytosis.

Hepatic cellular stress response pathways exhibit species differences in basal and inducible activity

This study compares hepatic stress response pathways in humans and preclinical animal species, finding rodents have greater basal and adaptive capacity for mitigating chemical insults.

Dysregulation of xenobiotic metabolism and mitochondrial dysfunction exacerbate acetaminophen-induced hepatotoxicity in human antigen R-deficient male mice

This study shows that HuR deficiency in male mice increases susceptibility to APAP-induced liver injury by impairing xenobiotic metabolism and mitochondrial function.

Integration of In Vitro and In Silico Approaches Enables Prediction of Drug-Induced Liver Injury

Dividing Cmax by lowest in vitro toxicity potency separates drugs by liver-injury (DILI) risk, AUC up to 96%; PBK-predicted Cmax without clinical data reaches 91%.

Diploid Hepatocytes Resist Acetaminophen-Induced Liver Injury Through Suppressed JNK Signaling

The paper shows diploid hepatocytes are more resistant to acetaminophen-induced liver injury due to reduced JNK signaling and mitochondrial damage.

Oxidation-Driven mtDNA B-Z Transition Activates ZBP1 to Mediate Acetaminophen Hepatotoxicity

This study identifies oxidative mtDNA B-Z transitions activating ZBP1 as a key mechanism in APAP-induced liver failure and shows TH107854 can reverse this process.

Direct contact between iPSC-derived macrophages and hepatocytes drives reciprocal acquisition of Kupffer cell identity and hepatocyte maturation

This study shows that co-culturing iPSC-derived macrophages with hepatocytes enhances macrophage maturation and hepatocyte function through direct cell-cell contact.

Systemic aldehyde storm induced by allyl alcohol exposure results in extensive hepatic ferroptosis in Aldh2*2 knock-in mice

This study shows that Aldh2*2 knock-in mice exposed to allyl alcohol experience a systemic aldehyde storm leading to hepatic ferroptosis due to impaired aldehyde detoxification.

Degradation rather than disassembly of necrotic debris is essential to enhance recovery after acute liver injury

This study shows that enzymatic degradation of necrotic debris improves recovery after liver injury, while disassembly strategies like peptide treatment or plasmin activation are less effective or harmful.

The Lipidome Landscape of Amiodarone Toxicity: An in vivo Lipid-centric Multi-Omics Study

This study investigates amiodarone toxicity in rats using lipidomics and transcriptomics, revealing significant lipidome and gene expression changes associated with hepatotoxicity.

Endoplasmic reticulum stress inhibition preserves mitochondrial function and cell survival during early onset of isoniazid-induced oxidative stress

This study investigates INH-induced hepatotoxicity, showing ER stress inhibition can mitigate oxidative stress and mitochondrial dysfunction during early exposure.

Protective Effect of 2-Hydroxyestrone and2-Hydroxyestradiol Against Chemically-Induced Hepatotoxicity In Vitro and In Vivo

This study shows that 2-hydroxyestrone and 2-hydroxyestradiol protect against ferroptosis in hepatoma cells and acetaminophen-induced liver injury by inhibiting PDI activity and reducing NO, ROS, and lipid-ROS accumulation.

Acetaminophen Overdose Reveals Protease-Activated Receptor 4 as a Low-Expressing but Potent Receptor on the Hepatic Endothelium

This study investigates the role of protease-activated receptors 1 and 4 on hepatic endothelial cells during acetaminophen overdose, finding that low-expressing PAR4 is a potent receptor with functional redundancy to PAR1.

BML-257, a small molecule that protects against drug induced liver injury in zebrafish

The paper identifies BML-257, a small molecule AKT inhibitor, that protects against drug-induced liver injury in zebrafish models.

DILIc: An AI-based classifier to search for Drug-Induced Liver Injury literature

This paper introduces DILIc, an AI classifier that identifies Drug-Induced Liver Injury literature using NLP and ML, achieving high accuracy in cross-validation and external validation.

Deriving time-concordant event cascades from gene expression data: A case study for Drug-Induced Liver Injury (DILI)

The paper develops a framework to identify time-concordant gene expression events in DILI using time-resolved transcriptomics and applies it to rat liver data from TG-GATEs to derive mechanistic hypotheses.

Contextualization of causal regulatory networks from toxicogenomics data applied to drug-induced liver injury

The paper applies a causal network tool to toxicogenomics data to infer regulatory networks in drug-induced liver injury, identifying conserved pathways between rat and human models.

Machine characterization of rat toxin responses identifies disease states, tolerance mechanisms and organ to whole-body communication

The paper uses machine learning to analyze toxicogenomic data and identifies toxin-induced disease states, tolerance mechanisms, and organ-to-whole-body communication in rats.