Allyl isothiocyanate (AITC) inhibits pregnane X receptor (PXR) and constitutive androstane receptor (CAR) activation and protects against acetaminophen- and amiodarone-induced cytotoxicity

• Published in: Archives of Toxicology Vol. 89; no. 1; pp. 57 - 72
• Main Authors: Lim, Yun-Ping, Cheng, Ching-Hao, Chen, Wei-Cheng, Chang, Shih-Yu, Hung, Dong-Zong, Chen, Jih-Jung, Wan, Lei, Ma, Wei-Chih, Lin, Yu-Hsien, Chen, Cing-Yu, Yokoi, Tsuyoshi, Nakajima, Miki, Chen, Chao-Jung
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Science and Business Media LLC 01.01.2015; Springer Berlin Heidelberg; Springer Nature B.V
• Subjects: Acetaminophen; Acetaminophen - metabolism; Acetaminophen - toxicity; Amiodarone; Amiodarone - metabolism; Amiodarone - toxicity; Animals; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cell Differentiation; Cell Differentiation - drug effects; Cell Line, Tumor; Cell Survival; Cell Survival - drug effects; Constitutive Androstane Receptor; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2B6 - genetics; Cytochrome P-450 CYP2B6 - metabolism; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A - genetics; Cytochrome P-450 CYP3A - metabolism; Cytotoxicity; Drug therapy; Environmental Health; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Enzymologic - drug effects; Humans; Isothiocyanates; Isothiocyanates - pharmacology; Mice; Molecular Toxicology; Neurons; Occupational Medicine/Industrial Medicine; Pharmacology/Toxicology; Pregnane X Receptor; Receptors, Cytoplasmic and Nuclear; Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Steroid; Receptors, Steroid - antagonists & inhibitors; Receptors, Steroid - genetics; Reverse Transcriptase Polymerase Chain Reaction; Transcriptional Activation; Transfection; Inducer–drug interaction; Drug-induced cytotoxicity; Pregnane X receptor; Allyl isothiocyanate; Constitutive androstane receptor; Cytochrome P450 3A4; Cytochrome P450 2B6

Antagonizing the action of the pregnane X receptor (PXR) may have important clinical implications for preventing inducer–drug interactions and improving therapeutic efficacy. We identified a widely distributed isothiocyanate, allyl isothiocyanate (AITC), which acts as an effective antagonist of the...