Abstract
N,N-Dimethylformamide (DMF) is an organic solvent extensively used in industries such as synthetic leather, fibers and films, and induces liver toxicity and carcinogenesis. Despite a series of experimental and clinical reports on DMF-induced liver failure, the mechanism of toxicity is yet unclear. This study investigated whether DMF in combination with a low dose of hepatotoxicant enhances hepatotoxicity, and if so, on what mechanistic basis. Treatment of rats with either DMF (50-500mg/kg/day, for 3 days) or a single low dose of CCl(4) (0.2ml/kg) alone caused small increases in plasma transaminases and lactate dehydrogenase activities. However, combinatorial treatment of DMF with CCl(4) markedly increased blood biochemical changes. Histopathology confirmed the synergism in hepatotoxicity. Moreover, DMF+CCl(4) caused PARP cleavage and caspase-3 activation, but decreased the level of Bcl-xL, all of which confirmed apoptosis of hepatocytes. Consistently, DMF+CCl(4) treatment markedly increased lipid peroxidation. By contrast, treatment of DMF in combination with lipopolysaccharide, acetaminophen or d-galactosamine caused no enhanced hepatotoxicity. Given the link between endoplasmic reticulum (ER) dysfunction and cell death, ER st...Continue Reading
References
Feb 11, 1978·Lancet·C P Chivers
Nov 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·C GalanosW Reutter
May 1, 1988·Annals of Internal Medicine·C A RedlichM R Cullen
Jan 1, 1986·Critical Reviews in Toxicology·G L Kennedy
Aug 1, 1984·Chemico-biological Interactions·V Scailteur, R Lauwerys
Sep 1, 1994·Journal of Clinical Gastroenterology·W M Cassidy, T B Reynolds
Feb 24, 1999·International Archives of Occupational and Environmental Health·R Wrbitzky
Mar 3, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·R F StachlewitzR G Thurman
Aug 7, 1999·The Journal of Biological Chemistry·A H BoularesM Smulson
Feb 7, 2001·Molecular and Cellular Biology·K D McCulloughN J Holbrook
May 18, 2001·International Archives of Occupational and Environmental Health·T NomiyamaK Omae
May 31, 2001·Journal of Occupational and Environmental Medicine·J C LuoM J Chang
May 16, 2002·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jaspreet S GujralHartmut Jaeschke
Jun 4, 2002·Nature Reviews. Molecular Cell Biology·Randal J KaufmanStacey M Arnold
Mar 26, 2003·Toxicological Sciences : an Official Journal of the Society of Toxicology·D W LynchM J Ryan
Oct 25, 2003·Journal of Cell Science·Michael J Thomenius, Clark W Distelhorst
Feb 7, 2004·Cell Death and Differentiation·R V RaoD E Bredesen
Oct 4, 2005·The Journal of Clinical Investigation·Chunyan XuJohn C Reed
Nov 26, 2005·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·J-C LuoM J W Chang
Feb 1, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Vito Racanelli, Barbara Rehermann
May 2, 2006·Chemico-biological Interactions·Young Woo KimSang Geon Kim
May 27, 2006·Journal of Gastroenterology and Hepatology·Sathish Kumar NatarajanKunissery A Balasubramanian
Apr 17, 2007·Journal of Hepatology·Shinichiro HanadaMichio Sata
Nov 6, 2007·Antioxidants & Redox Signaling·Jyoti D Malhotra, Randal J Kaufman
Dec 19, 2007·The Journal of Biological Chemistry·Makiko YokouchiMasanori Kitamura
Jul 21, 2009·Free Radical Biology & Medicine·Young Woo KimSang Geon Kim
Sep 30, 2009·European Journal of Pharmacology·Hongyang ShiLi Zhang
Citations
Sep 21, 2010·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Philippe HantsonRobert Garnier
Dec 3, 2014·Experimental and Molecular Pathology·Astrid KleberTobias Fink
Feb 2, 2016·Scientific Reports·Yuan ZhengJianmei Lu
Nov 15, 2011·Journal of Hazardous Materials·S Sanjeev KumarT B Karegoudar
Jul 27, 2011·Environmental Toxicology and Pharmacology·Ding RuiYang Yongjian
Oct 15, 2013·Liver International : Official Journal of the International Association for the Study of the Liver·Shengdong WangJie Bai
Dec 15, 2010·Journal of Hepatology·Harmeet Malhi, Randal J Kaufman
Sep 3, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Deshi DongJinyong Peng
Jun 1, 2011·Safety and Health at Work·Tae Hyun Kim, Sang Geon Kim
May 16, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Zhijun WuJuan Cheng
Mar 21, 2018·Journal of Molecular Endocrinology·Liping LuoFeng Liu
Dec 15, 2017·Dose-response : a Publication of International Hormesis Society·Jihong ZhangGuoxiong Xu
Jun 21, 2018·Biological Chemistry·Anna L Lang, Juliane I Beier
Sep 28, 2012·Critical Reviews in Toxicology·Gerald L Kennedy
Jan 5, 2014·Toxicological Research·Ki-Woong Kim, Yong Hyun Chung
Jul 11, 2020·Journal of Applied Toxicology : JAT·Zhen ZhangQing Wang
Apr 30, 2017·Scientific Reports·Jixiang FanJianmei Lu
Jul 8, 2020·Medicine·Zhi-Yong HuZeng-Li Zhang
Jan 1, 2016·Molecular Medicine Reports·Min WangMingyue Tan
Dec 27, 2019·Journal of Applied Toxicology : JAT·Hongmei JiangQing Wang
Jul 30, 2020·Food Science & Nutrition·Takahide Kariya, Yasushi Hasegawa
Aug 23, 2020·Ecotoxicology and Environmental Safety·Lin XuDianke Yu