Upstream eventCell injury/death
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding|
|IKK complex inhibition leading to liver injury||adjacent||High||High|
|Mitochondrial complex inhibition leading to liver injury||adjacent||Not Specified||Not Specified|
Life Stage Applicability
Key Event Relationship Description
Cell death can help the maintenance of the organ, for example by avoiding cancer. However, in the KER, cell death will lead to necrotic tissue. If too many cells die, the tissue will fall apart.
There are several types of necrotic tissue caused by cell death:
Apoptosis (individual cell necrosis), spotty and focal necrosis, zonal necrosis confluent necrosis. Every type can have a different underlying disease. All types can occur by drug induced liver injury.(Krishna 2017).
Evidence Supporting this KER
It has been well established that cell death can lead to necrotic tissue.
(Guicciardi et al. 2013): Apoptosis and necrosis in the liver.
(Luedde et al. 2014): Cell death in liver disease.
Uncertainties and Inconsistencies
Quantitative Understanding of the Linkage
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Krishna, M., 2017. Patterns of Necrosis in Liver Disease. , 10(2), pp.53–56.
Guicciardi, M.E. et al., 2013. Apoptosis and Necrosis in the Liver. Comprehensive Physiology, 3(2), pp.977–1010. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3867948&tool=pmcentrez&rendertype=abstract.
Luedde, T., Kaplowitz, N. & Schwabe, R.F., 2014. Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance. Gastroenterology., 14(11), pp.871–882.