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.

中文翻译：

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利福平激活AMPK，减轻Nrf2信号传导介导的肝脏氧化应激。

尽管利福平可能具有肝毒性作用，但也表明该化学物质可作为细胞保护剂抵抗氧化应激。因此，我们想知道利福平是否在肝脏中具有抗氧化剂之类的有益作用，因为某些药物的功效有时与它们的毒性以及保护作用有关。本研究旨在研究利福平在体外和体内对花生四烯酸（AA）加铁（AA +铁）协同处理和对乙酰氨基酚（APAP，500 mg / kg）诱导的氧化应激的抗氧化作用。在体内，口服利福平（100或200 mg / kg）可减轻血清丙氨酸氨基转移酶（ALT）和天冬氨酸转氨酶（AST），血清肝损伤标志物的水平，以对抗APAP治疗，并且在组织学上，改善组织损伤。在体外检查中，MTT分析用于评估利福平对AA +铁诱导的氧化应激的细胞死亡抑制作用。此外，DCFH-DA和Rh 123染色显示，利福平处理减少了AA +铁处理所引起的活性氧（ROS）产生和线粒体膜损伤。此外，我们探讨了利福平治疗是否通过激活AMPKα的上游激酶肝激酶B1（LKB1）来增强AMP激活的蛋白激酶（AMPK）的磷酸化。激活的AMPKα诱导核因子红系2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）的激活，这些蛋白在氧化还原平衡中起作用。此外，我们证实了在化合物C（一种AMPK抑制剂）处理下，利福平具有相反的细胞保护作用。