Related Experiment Video
Updated: May 23, 2025

Partial Lobular Hepatectomy: A Surgical Model for Morphologic Liver Regeneration
Published on: May 31, 2018
Autophagy, a novel player in acetaminophen (APAP)-induced hepatotoxicity
Hui Ye1, Francisco Javier Cubero2,3,4
1Department of Anesthesiology, ZhongDa Hospital Southeast University, 210009 Nanjing, China.
Abstract:
Acetaminophen (APAP), a widely used analgesic drug, is safe at therapeutic doses, but can produce significant hepatotoxicity upon overdose. Emerging evidence suggested that endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are key mechanisms in APAP-mediated hepatotoxicity. While ER stress-UPR and macroautophagy/autophagy appear to be independent cellular processes, we found a cross-linked mechanism in APAP liver injury. The specific ablation in liver parenchyma of XBP1 (X-box binding protein 1), a transcription factor mediating ER stress, mitigates APAP-induced liver injury. Interestingly, this mechanism is linked to enhanced autophagy which seems to be responsible for the modulation of the enzymatic activity of CYP2E1, which is involved in the metabolic conversion of APAP, and ultimately protects liver against APAP toxicity. Altogether, our study highlighted autophagy as a novel player in the pathophysiology of APAP-induced liver injury and opened new therapeutic avenues for its modulation in patients with drug overdose.
More Related Videos
Related Concept Videos
Phase II Reactions: Acetylation Reactions
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
Autophagy
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Delivery Pathways to the Lysosome
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...

