PMID- 36110535
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220917
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Co-Treatment With Resveratrol and FGF1 Protects Against Acute Liver Toxicity 
      After Doxorubicin Treatment via the AMPK/NRF2 Pathway.
PG  - 940406
LID - 10.3389/fphar.2022.940406 [doi]
LID - 940406
AB  - Doxorubicin (DOX), an anthracycline type of chemotherapy, is an effective therapy 
      for several types of cancer, but serious side effects, such as severe 
      hepatotoxicity, limit its use currently. Accordingly, an effective therapeutic 
      strategy to prevent DOX-related hepatotoxicity is urgently needed. Through the 
      inhibition of oxidative stress, fibroblast growth factor 1 (FGF1) is an effect 
      therapy for a variety of liver diseases, but its use is limited by an increased 
      risk of tumorigenesis due to hyperproliferation. Resveratrol (RES), a natural 
      product, inhibits the growth of many cancer cell lines, including liver, breast, 
      and prostate cancer cells. Therefore, this study explored whether and how RES in 
      combination with FGF1 can alleviate DOX-induced hepatotoxicity. The results 
      showed that RES or FGF1 alone improved DOX-induced hepatic inflammation, 
      apoptosis and oxidative stress, and these adverse effects were further attenuated 
      after treatment with both RES and FGF1. Mechanistically, both in vivo and in 
      vitro results showed that RES/FGF1 reduced oxidative stress and thereby 
      alleviated liver injury by promoting nuclear translocation of nuclear factor 
      erythroid 2-related factor 2 (NRF2) and subsequently upregulating expression of 
      antioxidant proteins in an adenosine monophosphate-activated protein kinase 
      (AMPK)-dependent manner. Together, our results not only demonstrate that 
      co-treatment with RES and FGF1 significantly inhibited DOX-induced hepatic 
      inflammation and apoptosis, but also that co-treatment with RES and FGF1 markedly 
      suppressed DOX-induced hepatic oxidative stress, via targeting the AMPK/NRF2 
      pathway and subsequently ameliorating hepatic dysfunction. Thus, the combination 
      of RES and FGF1 may provide a new therapeutic strategy for limiting DOX-induced 
      hepatotoxicity.
CI  - Copyright (c) 2022 Xu, Liu, Li, Xiao, Gao, Zhang, Lu, Wang, Guo, Wen and Gu.
FAU - Xu, Xianchou
AU  - Xu X
AD  - Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong 
      University, Jinan, China.
AD  - Department of Gastrointestinal Surgery, Pingyang Affiliated Hospital of Wenzhou 
      Medical University, Wenzhou, China.
FAU - Liu, Qingbo
AU  - Liu Q
AD  - School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong 
      University, Jinan, China.
FAU - Li, Jiahao
AU  - Li J
AD  - School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong 
      University, Jinan, China.
FAU - Xiao, Mengjie
AU  - Xiao M
AD  - School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong 
      University, Jinan, China.
FAU - Gao, Ting
AU  - Gao T
AD  - School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong 
      University, Jinan, China.
FAU - Zhang, Xiaohui
AU  - Zhang X
AD  - School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong 
      University, Jinan, China.
FAU - Lu, Guangping
AU  - Lu G
AD  - School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong 
      University, Jinan, China.
FAU - Wang, Jie
AU  - Wang J
AD  - School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong 
      University, Jinan, China.
FAU - Guo, Yuanfang
AU  - Guo Y
AD  - School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong 
      University, Jinan, China.
FAU - Wen, Peinan
AU  - Wen P
AD  - Department of Gastrointestinal Surgery, Pingyang Affiliated Hospital of Wenzhou 
      Medical University, Wenzhou, China.
FAU - Gu, Junlian
AU  - Gu J
AD  - School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong 
      University, Jinan, China.
LA  - eng
PT  - Journal Article
DEP - 20220830
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9468578
OTO - NOTNLM
OT  - AMPK
OT  - NRF2
OT  - doxorubicin
OT  - hepatotoxicity
OT  - oxidative stress
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/09/17 06:00
MHDA- 2022/09/17 06:01
PMCR- 2022/08/30
CRDT- 2022/09/16 02:34
PHST- 2022/05/10 00:00 [received]
PHST- 2022/06/22 00:00 [accepted]
PHST- 2022/09/16 02:34 [entrez]
PHST- 2022/09/17 06:00 [pubmed]
PHST- 2022/09/17 06:01 [medline]
PHST- 2022/08/30 00:00 [pmc-release]
AID - 940406 [pii]
AID - 10.3389/fphar.2022.940406 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Aug 30;13:940406. doi: 10.3389/fphar.2022.940406. 
      eCollection 2022.