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Rifampicin Activates AMPK and Alleviates Oxidative Stress in the Liver as Mediated With Nrf2 Signaling

Rifampicin Activates AMPK and Alleviates Oxidative Stress in the Liver as Mediated With Nrf2 Signaling

Eun Hye Lee, Su Youn Baek, Ji Young Park, Young Woo Kim

Chem Biol Interact. 2020 Jan 5;315:108889.

PMID: 31678598

Abstract:

Although rifampicin could have a hepatic toxic effect, it has also been shown that this chemical acts as a cellular protectant against oxidative stress. Therefore, we wondered whether rifampicin has a beneficial effect such as an anti-oxidant in the liver, because the efficacy of some drugs sometimes relates with their toxicity as well as protective effects. The present study aimed to investigate the antioxidant effect of rifampicin against arachidonic acid (AA) plus iron (AA + iron) cotreatment and against acetaminophen (APAP, 500 mg/kg)-induced oxidative stress, in vitro and in vivo, respectively. In vivo, oral administration of rifampicin (100 or 200 mg/kg) attenuated elevation of serum alanine aminotransferase (ALT) and aspartate transaminase (AST), serum liver injury markers, against APAP treatment and, histologically, ameliorated tissue damage. Under in vitro examination, MTT assays were used to assess the cell death inhibitory effect of rifampicin against AA + iron-induced oxidative stress. In addition, DCFH-DA and Rh 123 staining showed that rifampicin treatment reduced reactive oxygen species (ROS) production and mitochondrial membrane damage, which had been induced by AA + iron treatment. Further, we explored whether rifampicin treatment enhanced phosphorylation of AMP-activated protein kinase (AMPK) by activation of liver kinase B1 (LKB1), the upstream kinase of AMPKα. Activated AMPKα induced activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), which are proteins functioning in redox balance. Moreover, we confirmed a reversed cell protective effect of rifampicin under compound C (an AMPK inhibitor) treatment. Overall, our data demonstrate that rifampicin effectively protects the liver against cellular oxidative stress through AMPKα and Nrf2 pathway.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP614802-A	Acetaminophen Related Compound C		614-80-2	Price

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