Role and mechanisms of autophagy in acetaminophen-induced liver injury.
Xiaojuan ChaoHua WangHartmut JaeschkeWen-Xing DingPublished in: Liver international : official journal of the International Association for the Study of the Liver (2018)
Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure in the USA and many other countries. Although the metabolism and pathogenesis of APAP has been extensively investigated for decades, the mechanisms by which APAP induces liver injury are incompletely known, which hampers the development of effective therapeutic approaches to tackle this important clinical problem. Autophagy is a highly conserved intracellular degradation pathway, which aims at recycling cellular components and damaged organelles in response to adverse environmental conditions and stresses as a survival mechanism. There is accumulating evidence indicating that autophagy is activated in response to APAP overdose in specific liver zone areas, and pharmacological activation of autophagy protects against APAP-induced liver injury. Increasing evidence also suggests that hepatic autophagy is impaired in nonalcoholic fatty livers (NAFLD), and NAFLD patients are more susceptible to APAP-induced liver injury. Here, we summarized the current progress on the role and mechanisms of autophagy in protecting against APAP-induced liver injury.
Keyphrases
- liver injury
- cell death
- liver failure
- endoplasmic reticulum stress
- drug induced
- signaling pathway
- oxidative stress
- end stage renal disease
- chronic kidney disease
- emergency department
- ejection fraction
- newly diagnosed
- intensive care unit
- mass spectrometry
- respiratory failure
- adverse drug
- electronic health record
- atomic force microscopy