Oleanolic Acid-Mediated Inhibition of Pregnane X Receptor and Constitutive Androstane Receptor Attenuates Rifampin-Isoniazid Cytotoxicity

• Published in: Journal of agricultural and food chemistry Vol. 65; no. 39; pp. 8606 - 8616
• Main Authors: Lin, Yen-Ning, Chen, Chao-Jung, Chang, Hsiao-Yun, Cheng, Wai-Kok, Lee, Ying-Ray, Chen, Jih-Jung, Lim, Yun-Ping
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 04.10.2017
• Subjects: adverse effects; antagonists; catalytic activity; Cell Line; cytochrome P-450; Cytochrome P-450 CYP2B6 - genetics; Cytochrome P-450 CYP2B6 - metabolism; Cytochrome P-450 CYP3A - genetics; Cytochrome P-450 CYP3A - metabolism; Cytochrome P-450 CYP3A Inhibitors - pharmacology; cytotoxicity; Drug Interactions; drugs; Gene Expression Regulation, Enzymologic - drug effects; Hep G2 Cells; Hepatocytes - drug effects; Humans; isoniazid; Isoniazid - toxicity; oleanolic acid; Oleanolic Acid - pharmacology; probability; Promoter Regions, Genetic - drug effects; Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors; Receptors, Steroid - antagonists & inhibitors; rifampicin; Rifampin - toxicity; rodents; Species Specificity; transcription (genetics); transcriptional activation; pregnane X receptor; isoniazid; cytochrome P450; constitutive androstane receptor; oleanolic acid; rifampin

Interactions between transcriptional inducers of cytochrome P450 (CYP450) and pharmacological agents might decrease drug efficacy and induce side effects. Such interactions could be prevented using an antagonist of the pregnane X receptor (PXR) and constitutive androstane receptor (CAR). Here, we ai...