TY - JOUR
T1 - Nrf2 in liver toxicology
AU - Taguchi, Keiko
AU - Kensler, Thomas W.
N1 - Funding Information:
This work was supported by funding from MEXT/JSPS KAKENHI (16H01190 to K.T.); TERUMO LIFE SCIENCES FOUNDATION (18-III415 to K.T.) as well as NIH Grant R35 CA197222 (T.W.K) and the Washington State Andy Hill CARE Fund (T.W.K.).
Funding Information:
This work was supported by funding from MEXT/JSPS KAKENHI (16H01190 to K.T.); TERUMO LIFE SCIENCES FOUNDATION (18-III415 to K.T.) as well as NIH Grant R35 CA197222 (T.W.K) and the Washington State Andy Hill CARE Fund (T.W.K.).
Publisher Copyright:
© 2019, The Pharmaceutical Society of Korea.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Liver plays essential roles in the metabolism of many endogenous chemicals and exogenous toxicants. Mechanistic studies in liver have been at the forefront of efforts to probe the roles of bioactivation and detoxication of environmental toxins and toxicants in hepatotoxicity. Moreover, idiosyncratic hepatoxicity remains a key barrier in the clinical development of drugs. The now vast Nrf2 field emerged in part from biochemical and molecular studies on chemical inducers of hepatic detoxication enzymes and subsequent characterization of the modulation of drug/toxicant induced hepatotoxicities in mice through disruption of either Nrf2 or Keap1 genes. In general, loss of Nrf2 increases the sensitivity to such toxic chemicals, highlighting a central role of this transcription factor and its downstream target genes as a modifier to chemical stress. In this review, we summarize the impact of Nrf2 on the toxicology of multiple hepatotoxicants, and discuss efforts to utilize the Nrf2 response in predictive toxicology.
AB - Liver plays essential roles in the metabolism of many endogenous chemicals and exogenous toxicants. Mechanistic studies in liver have been at the forefront of efforts to probe the roles of bioactivation and detoxication of environmental toxins and toxicants in hepatotoxicity. Moreover, idiosyncratic hepatoxicity remains a key barrier in the clinical development of drugs. The now vast Nrf2 field emerged in part from biochemical and molecular studies on chemical inducers of hepatic detoxication enzymes and subsequent characterization of the modulation of drug/toxicant induced hepatotoxicities in mice through disruption of either Nrf2 or Keap1 genes. In general, loss of Nrf2 increases the sensitivity to such toxic chemicals, highlighting a central role of this transcription factor and its downstream target genes as a modifier to chemical stress. In this review, we summarize the impact of Nrf2 on the toxicology of multiple hepatotoxicants, and discuss efforts to utilize the Nrf2 response in predictive toxicology.
KW - Hepatocarcinogenesis
KW - Hepatoxicity
KW - Keap1
KW - Nrf2
KW - Xenobiotic metabolism
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U2 - 10.1007/s12272-019-01192-3
DO - 10.1007/s12272-019-01192-3
M3 - Review article
C2 - 31782059
AN - SCOPUS:85075656308
SN - 0253-6269
VL - 43
SP - 337
EP - 349
JO - Archives of Pharmacal Research
JF - Archives of Pharmacal Research
IS - 3
ER -
