Metformin ameliorates arsenic trioxide hepatotoxicity via inhibiting mitochondrial complex I

Cell Death & Disease
Sunbin LingXiao Xu

Abstract

Arsenic trioxide (ATO) is a well-accepted chemotherapy agent in managing promyelocytic leukemia. ATO often causes severe health hazards such as hepatotoxicity, dermatosis, neurotoxicity, nephrotoxicity and cardiotoxicity. The production of reactive oxygen species, (ROS) play a significant role in ATO-induced hepatotoxicity. The oral hypoglycemic drug, metformin, is considered to be a potential novel agent for chemoprevention in the treatment of cancer. Moreover, metformin has also been shown to have hepatoprotective effects. In the present study, we demonstrated that metformin protected normal hepatocytes from ATO-induced apoptotic cell death in vitro and in vivo. Gene expression screening revealed that glucose metabolism might be related to the metformin-induced protective effect on ATO-treated AML12 cells. The metformin-promoted or induced glycolysis was not responsible for the protection of AML12 cells from ATO-induced apoptotic cell death. Instead, metformin increased the intracellular NADH/NAD+ ratio by inhibiting mitochondrial respiratory chain complex I, further decreasing the intracellular ROS induced by ATO. Treatment with low glucose or rotenone, a mitochondrial respiratory chain complex I inhibitor, also protected AM...Continue Reading

References

Sep 1, 1985·In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association·D AcostaM A Smith
Aug 28, 1998·Science·D R Green, J C Reed
May 30, 2006·Journal of Bioenergetics and Biomembranes·Cécile BatandierXavier M Leverve
Jul 11, 2006·Biochimica Et Biophysica Acta·Giorgio LenazAnnalisa Biondi
Jan 8, 2008·Cell Metabolism·Ralph J DeBerardinisCraig B Thompson
Feb 26, 2008·Experimental Biology and Medicine·Jun WuQing Yang
Dec 28, 2012·Biochimica Et Biophysica Acta·Lea Bleier, Stefan Dröse
Jan 12, 2013·Trends in Biochemical Sciences·Kevin MoreauDavid C Rubinsztein
Jul 12, 2013·The New England Journal of Medicine·Francesco Lo-CocoUNKNOWN Study Alliance Leukemia
Nov 10, 2013·PloS One·Enza LonardoChristopher Heeschen
May 7, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xiaodan ZhangRoongruedee Chaiteerakij
May 16, 2014·Journal of Gastrointestinal Cancer·Pochi R Subbarayan, Bach Ardalan
May 21, 2014·ELife·William W WheatonNavdeep S Chandel
Jun 4, 2014·Proceedings of the National Academy of Sciences of the United States of America·Wouter De HaesLiesbet Temmerman
Aug 8, 2014·Cell Metabolism·Joseph A Baur, Morris J Birnbaum
Oct 11, 2014·The Biochemical Journal·Eric Fontaine
Dec 11, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xuejun YangLiming Wang
Feb 11, 2015·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Tingting FengYan Li
Mar 17, 2015·Nature Cell Biology·Lindsey K Boroughs, Ralph J DeBerardinis
May 17, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sasidharan Padmaja DivyaZhuo Zhang
Jul 28, 2015·Biochemical Pharmacology·Ravirajsinh N JadejaNeeraj Kumar Saxena
Sep 19, 2015·The Lancet Oncology·Alan K BurnettUNKNOWN UK National Cancer Research Institute Acute Myeloid Leukaemia Working Group
Oct 23, 2015·Cell Reports·Chen-Fang LeeJonathan D Powell
Nov 17, 2015·Biochimica Et Biophysica Acta·Andrei D Vinogradov, Vera G Grivennikova
Nov 26, 2015·Environmental Toxicology and Pharmacology·Nafiseh Sadat AlamolhodaeiGholamreza Karimi
Jan 12, 2016·British Journal of Pharmacology·Bhaskar BhattacharyaRichie Soong
Apr 6, 2016·Medycyna pracy·Karolina Kulik-KupkaBarbara Zubelewicz-Szkodzińska

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Citations

Oct 13, 2018·Thoracic Cancer·Miao Chen, Songbo Xie
Jul 22, 2018·Current Medicinal Chemistry·Aysegul HanikogluTomris Ozben
Sep 6, 2019·Apoptosis : an International Journal on Programmed Cell Death·Mengqiu WuZhanjun Jia
Sep 11, 2019·Animals : an Open Access Journal From MDPI·Ahmed M AlmalkiAyman M Mahmoud
Dec 5, 2019·Animals : an Open Access Journal From MDPI·Ahmed M AlmalkiAyman M Mahmoud
Feb 9, 2020·Biomolecules·Yuxin HuYuanyuan Xu
Dec 11, 2019·Molecular Biology Reports·Mohamed A DkhilSaleh Al-Quraishy
Dec 23, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Mengke YuanJundong Wang
Feb 11, 2021·Biological Trace Element Research·Chandra PrakashVijay Kumar
Apr 4, 2021·Biomedicines·Juan M Suárez-RiveroJosé A Sánchez-Alcázar
Jan 29, 2019·European Journal of Pharmacology·Hiromi SatoAkihiro Hisaka
Feb 13, 2019·European Journal of Pharmacology·Milad IranshahyGholamreza Karimi
May 25, 2021·Saudi Journal of Biological Sciences·Adel F TohamyHassan A Hemeg
Jun 9, 2021·Neural Regeneration Research·Ahmad Alhowail, Sridevi Chigurupati
May 12, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Hu HuaGuixia Ding

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Methods Mentioned

BETA
fluorescence microscopy
flow cytometry

Software Mentioned

Image
Image Lab
SPSS
Pro Plus
Seahorse

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