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Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis
Drug-induced liver injury (DILI) can broadly be divided into predictable and dose dependent such as acetaminophen (APAP) and unpredictable or idiosyncratic DILI (IDILI). Liver injury from drug hepatotoxicity (whether idiosyncratic or predictable) results in hepatocyte cell death and inflammation. Th...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454931/ https://www.ncbi.nlm.nih.gov/pubmed/28486401 http://dx.doi.org/10.3390/ijms18051018 |
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author | Iorga, Andrea Dara, Lily Kaplowitz, Neil |
author_facet | Iorga, Andrea Dara, Lily Kaplowitz, Neil |
author_sort | Iorga, Andrea |
collection | PubMed |
description | Drug-induced liver injury (DILI) can broadly be divided into predictable and dose dependent such as acetaminophen (APAP) and unpredictable or idiosyncratic DILI (IDILI). Liver injury from drug hepatotoxicity (whether idiosyncratic or predictable) results in hepatocyte cell death and inflammation. The cascade of events leading to DILI and the cell death subroutine (apoptosis or necrosis) of the cell depend largely on the culprit drug. Direct toxins to hepatocytes likely induce oxidative organelle stress (such as endoplasmic reticulum (ER) and mitochondrial stress) leading to necrosis or apoptosis, while cell death in idiosyncratic DILI (IDILI) is usually the result of engagement of the innate and adaptive immune system (likely apoptotic), involving death receptors (DR). Here, we review the hepatocyte cell death pathways both in direct hepatotoxicity such as in APAP DILI as well as in IDILI. We examine the known signaling pathways in APAP toxicity, a model of necrotic liver cell death. We also explore what is known about the genetic basis of IDILI and the molecular pathways leading to immune activation and how these events can trigger hepatotoxicity and cell death. |
format | Online Article Text |
id | pubmed-5454931 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-54549312017-06-08 Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis Iorga, Andrea Dara, Lily Kaplowitz, Neil Int J Mol Sci Review Drug-induced liver injury (DILI) can broadly be divided into predictable and dose dependent such as acetaminophen (APAP) and unpredictable or idiosyncratic DILI (IDILI). Liver injury from drug hepatotoxicity (whether idiosyncratic or predictable) results in hepatocyte cell death and inflammation. The cascade of events leading to DILI and the cell death subroutine (apoptosis or necrosis) of the cell depend largely on the culprit drug. Direct toxins to hepatocytes likely induce oxidative organelle stress (such as endoplasmic reticulum (ER) and mitochondrial stress) leading to necrosis or apoptosis, while cell death in idiosyncratic DILI (IDILI) is usually the result of engagement of the innate and adaptive immune system (likely apoptotic), involving death receptors (DR). Here, we review the hepatocyte cell death pathways both in direct hepatotoxicity such as in APAP DILI as well as in IDILI. We examine the known signaling pathways in APAP toxicity, a model of necrotic liver cell death. We also explore what is known about the genetic basis of IDILI and the molecular pathways leading to immune activation and how these events can trigger hepatotoxicity and cell death. MDPI 2017-05-09 /pmc/articles/PMC5454931/ /pubmed/28486401 http://dx.doi.org/10.3390/ijms18051018 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Iorga, Andrea Dara, Lily Kaplowitz, Neil Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis |
title | Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis |
title_full | Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis |
title_fullStr | Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis |
title_full_unstemmed | Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis |
title_short | Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis |
title_sort | drug-induced liver injury: cascade of events leading to cell death, apoptosis or necrosis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454931/ https://www.ncbi.nlm.nih.gov/pubmed/28486401 http://dx.doi.org/10.3390/ijms18051018 |
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