Bortezomib alleviates drug-induced liver injury by regulating CYP2E1 gene transcription

International Journal of Molecular Medicine
Woo-Jae ParkJoo-Won Park

Abstract

Acute liver failure, i.e., the fatal deterioration of liver function, is the most common indication that emergency liver transplantation is necessary. Moreover, in the USA, drug-induced liver injury (DILI), including acetaminophen (APAP)-induced hepatotoxicity, is the main cause of acute liver failure. Matching a donor for liver transplantation is extremely difficult, and thus the development of a novel therapy for DILI is urgently needed. Following recent approval by the FDA of the proteasomal inhibitor bortezomib, its therapeutic effects on various human diseases, including solid and hematologic malignancies, have been validated. However, the specific action of proteasomal inhibition in cases of DILI had not been elucidated prior to this study. To examine the effects of proteasomal inhibition in DILI experimentally, male C56Bl/6 mice were injected with 1 mg bortezomib/kg before APAP treatment. Bortezomib not only alleviated APAP-induced hepatotoxicity in a time- and dose-dependent manner, it also alleviated CCl4- and thioacetamide-induced hepatotoxicity. We also noted that bortezomib significantly reduced cytochrome P450 2E1 (CYP2E1) expression and activity in the liver, which was accompanied by the induction of endoplasmic r...Continue Reading

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Citations

Jun 18, 2019·Drug Metabolism Reviews·Jingxuan ChenJianjun Chen
Feb 23, 2020·Frontiers in Pharmacology·Siyu FuTaoyou Zhou
Feb 25, 2021·Bioscience, Biotechnology, and Biochemistry·Zhongyang DingBei Lu

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Methods Mentioned

BETA
PCR
electrophoresis
transfection

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