PMID- 32738495
OWN - NLM
STAT- MEDLINE
DCOM- 20210901
LR  - 20210901
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 161
DP  - 2020 Nov
TI  - Current etiological comprehension and therapeutic targets of 
      acetaminophen-induced hepatotoxicity.
PG  - 105102
LID - S1043-6618(20)31410-9 [pii]
LID - 10.1016/j.phrs.2020.105102 [doi]
AB  - Acetaminophen (APAP) is the most popular mild analgesic and antipyretic drug used 
      worldwide. APAP overdose leads to drug-induced hepatotoxicity and can cause 
      hepatic failure if treatment delayed. It is adequately comprehended that the 
      metabolism of high-dose APAP by cytochrome P450 enzymes generates 
      N-acetyl-p-benzoquinone imine (NAPQI), a toxic metabolite, which leads to 
      glutathione (GSH) depletion, oxidative stress, and activation of various complex 
      molecular pathways that initiate liver injury and downstream hepatic necrosis. 
      Administration of activated charcoal followed by N-acetylcysteine (NAC) is 
      considered the mainstay therapy; however, including side effects and limitation 
      of rescuing for the delayed patients where liver transplantation may be a 
      lifesaving procedure. Many complex signal transduction pathways such as c-Jun 
      NH(2)-terminal kinase (JNK), mammalian target of rapamycin (mTOR), nuclear factor 
      (NF)-kappaB, and NF (erythroid-derived 2)- like 2 (Nrf2) are involved in the 
      development of APAP hepatotoxicity, but yet hasn't been comprehensively studied; 
      thus, the search for effective antidotes and better management strategies 
      continues. Here, we reviewed the most current advances to elucidate the 
      etiological factors and therapeutic targets that could provide better strategies 
      for the management of APAP-induced hepatotoxicity.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Chowdhury, Apu
AU  - Chowdhury A
AD  - School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China.
FAU - Nabila, Jahan
AU  - Nabila J
AD  - School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China.
FAU - Adelusi Temitope, Isaac
AU  - Adelusi Temitope I
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, Jiangsu, China.
FAU - Wang, Sicen
AU  - Wang S
AD  - School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China. Electronic 
      address: wangsc@mail.xjtu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200730
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Antidotes)
RN  - 0 (Antioxidants)
RN  - 0 (Cytochrome P-450 Enzyme Inhibitors)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 362O9ITL9D (Acetaminophen)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - *Acetaminophen
MH  - Animals
MH  - Antidotes/*pharmacology
MH  - Antioxidants/pharmacology
MH  - Autophagy/drug effects
MH  - Chemical and Drug Induced Liver Injury/*drug 
      therapy/etiology/metabolism/pathology
MH  - Cytochrome P-450 Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Liver/*drug effects/metabolism/pathology
MH  - Liver Regeneration/drug effects
MH  - Molecular Targeted Therapy
MH  - NF-E2-Related Factor 2/agonists/metabolism
MH  - Oxidative Stress/drug effects
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Signal Transduction
OTO - NOTNLM
OT  - 4-Methylpyrazole (PubChem CID: 3406)
OT  - Acetaminophen
OT  - Acetaminophen (PubChem CID: 1983)
OT  - Autophagy
OT  - Glutathione (PubChem CID: 124886)
OT  - Hepatotoxicity
OT  - Isoproterenol (PubChem CID: 3779)
OT  - JNK
OT  - Mangiferin (PubChem CID: 5281647)
OT  - Metformin (PubChem CID: 4091)
OT  - N-acetylcysteine (PubChem CID: 12035)
OT  - NF-kappaB
OT  - Nrf2-ARE
OT  - Resolvin D2 (PubChem CID: 11383310)
EDAT- 2020/08/02 06:00
MHDA- 2021/09/02 06:00
CRDT- 2020/08/02 06:00
PHST- 2020/05/05 00:00 [received]
PHST- 2020/07/03 00:00 [revised]
PHST- 2020/07/21 00:00 [accepted]
PHST- 2020/08/02 06:00 [pubmed]
PHST- 2021/09/02 06:00 [medline]
PHST- 2020/08/02 06:00 [entrez]
AID - S1043-6618(20)31410-9 [pii]
AID - 10.1016/j.phrs.2020.105102 [doi]
PST - ppublish
SO  - Pharmacol Res. 2020 Nov;161:105102. doi: 10.1016/j.phrs.2020.105102. Epub 2020 
      Jul 30.