PMID- 33238403
OWN - NLM
STAT- MEDLINE
DCOM- 20210421
LR  - 20210421
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 12
IP  - 11
DP  - 2020 Nov 23
TI  - Allyl Isothiocyanate Protects Acetaminophen-Induced Liver Injury via NRF2 
      Activation by Decreasing Spontaneous Degradation in Hepatocyte.
LID - 10.3390/nu12113585 [doi]
LID - 3585
AB  - Acetaminophen (APAP) is one of the most frequently prescribed analgesic and 
      anti-pyretic drugs. However, APAP-induced hepatotoxicity is a major cause of 
      acute liver failure globally. While the therapeutic dose is safe, an overdose of 
      APAP produces an excess of the toxic metabolite N-acetyl-p-benzoquinone imine 
      (NAPQI), subsequently resulting in hepatotoxicity. Allyl isothiocyanate (AITC), a 
      bioactive molecule in cruciferous plants, is reported to exert various biological 
      effects, including anti-inflammatory, anti-cancer, and anti-microbial effects. 
      Notably, AITC is known for activating nuclear factor erythroid 2-related factor 2 
      (NRF2), but there is limited evidence supporting the beneficial effects on 
      hepatocytes and liver, where AITC is mainly metabolized. We applied a mouse model 
      in the current study to investigate whether AITC protects the liver against 
      APAP-induced injury, wherein we observed the protective effects of AITC. 
      Furthermore, NRF2 nuclear translocation and the increase of target genes by AITC 
      treatment were confirmed by in vitro experiments. APAP-induced cell damage was 
      attenuated by AITC via an NRF2-dependent manner, and rapid NRF2 activation by 
      AITC was attributed to the elevation of NRF2 stability by decreasing its 
      spontaneous degradation. Moreover, liver tissues from our mouse experiment 
      revealed that AITC increases the expression of heme oxygenase-1 (HO-1), an NRF2 
      target gene, confirming the potential of AITC as a hepatoprotective agent that 
      induces NRF2 activation. Taken together, our results indicate the potential of 
      AITC as a natural-product-derived NRF2 activator targeting the liver.
FAU - Kim, Min Woo
AU  - Kim MW
AUID- ORCID: 0000-0002-6597-4522
AD  - Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul 
      National University, Seoul 08826, Korea.
FAU - Kang, Ju-Hee
AU  - Kang JH
AUID- ORCID: 0000-0002-0192-6310
AD  - College of Pharmacy, Gachon University, Incheon 21936, Korea.
FAU - Jung, Hyun Jin
AU  - Jung HJ
AD  - College of Pharmacy, Gachon University, Incheon 21936, Korea.
FAU - Park, Se Yong
AU  - Park SY
AD  - Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul 
      National University, Seoul 08826, Korea.
FAU - Phan, Thu Han Le
AU  - Phan THL
AD  - College of Pharmacy, Gachon University, Incheon 21936, Korea.
FAU - Namgung, Hee
AU  - Namgung H
AD  - Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 
      21999, Korea.
FAU - Seo, Seung-Yong
AU  - Seo SY
AUID- ORCID: 0000-0002-2672-4707
AD  - College of Pharmacy, Gachon University, Incheon 21936, Korea.
FAU - Yoon, Yeo Sung
AU  - Yoon YS
AD  - Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul 
      National University, Seoul 08826, Korea.
FAU - Oh, Seung Hyun
AU  - Oh SH
AUID- ORCID: 0000-0003-3678-2772
AD  - College of Pharmacy, Gachon University, Incheon 21936, Korea.
LA  - eng
GR  - NRF-2019M3A9D5A01101025/National Research Foundation of Korea/
GR  - 2020R1A6A1A03043708/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20201123
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 0 (Isothiocyanates)
RN  - 362O9ITL9D (Acetaminophen)
RN  - BN34FX42G3 (allyl isothiocyanate)
SB  - IM
MH  - Acetaminophen/*adverse effects
MH  - Analgesics, Non-Narcotic/*adverse effects
MH  - Animals
MH  - Chemical and Drug Induced Liver Injury/*prevention & control
MH  - Disease Models, Animal
MH  - Hepatocytes/*drug effects
MH  - Isothiocyanates/*pharmacology
MH  - Liver/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
PMC - PMC7700243
OTO - NOTNLM
OT  - N-acetyl-p-aminophenol)
OT  - NRF2
OT  - acetaminophen (APAP
OT  - allyl isothiocyanate (AITC)
OT  - hepatotoxicity
COIS- The authors declare no conflict of interest.
EDAT- 2020/11/27 06:00
MHDA- 2021/04/22 06:00
PMCR- 2020/11/01
CRDT- 2020/11/26 01:00
PHST- 2020/09/30 00:00 [received]
PHST- 2020/11/13 00:00 [revised]
PHST- 2020/11/19 00:00 [accepted]
PHST- 2020/11/26 01:00 [entrez]
PHST- 2020/11/27 06:00 [pubmed]
PHST- 2021/04/22 06:00 [medline]
PHST- 2020/11/01 00:00 [pmc-release]
AID - nu12113585 [pii]
AID - nutrients-12-03585 [pii]
AID - 10.3390/nu12113585 [doi]
PST - epublish
SO  - Nutrients. 2020 Nov 23;12(11):3585. doi: 10.3390/nu12113585.