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Self-developed NF-κB inhibitor 270 protects against LPS-induced acute kidney injury and lung injury through improving inflammation
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  • Yanyan Yu,
  • Xiangqian Li,
  • Wenpeng Hu,
  • Shichao Cui,
  • Jiajia Dai,
  • Yanan Gao,
  • Yiting Zhang,
  • Jiaying Zhu,
  • Dayong Shi
Yanyan Yu
Shandong University
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Xiangqian Li
Shandong University
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Wenpeng Hu
Shandong University
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Shichao Cui
Shanghai Institute of Materia Medica Chinese Academy of Sciences
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Jiajia Dai
Shandong University
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Yanan Gao
Shandong University
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Yiting Zhang
Shandong University
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Jiaying Zhu
Shandong University
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Dayong Shi
Shandong University
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Abstract

Background and Purpose: Sepsis-induced acute kidney injury (AKI) and acute lung injury (ALI) have high morbidity and mortality, with no effective clinically available drugs. Anti-inflammation is effective strategy in the therapy of AKI and ALI. NF-κB is a target for the development of anti‑inflammatory agents. The purpose of the study is to evaluate the effect of 270, self-developed NF-κB inhibitor, in LPS-induced AKI and ALI. Experimental Approach: LPS-induced macrophages were used to examine the anti-inflammation activity of 270. Sepsis-induced AKI and ALI mice models were established by intraperitoneal injection of LPS (10 mg/kg) for 24 h. Oral administration 270 for 14 days before LPS stimulation. Plasma, kidney and lung tissues were collected and used for histopathology, biochemical assay, ELISA, RT-PCR, and western blot analyses. Key Results: In vitro, we showed that 270 suppressed the inflammation response in LPS-induced RAW 264.7 macrophages and bone marrow derived macrophages. In vivo, we found that 270 ameliorated LPS-induced AKI and ALI, as evidenced by improving various pathological changes, reducing the expression of pro-inflammation genes, blocking the activation of NF-κB and JNK pathways, attenuating the elevated myeloperoxidase (MPO) activity and malondialdehyde (MDA) content, ameliorating the activated ER stress, reversing the inhibition effect on autophagy in kidney and lung tissues, and alleviating the enhanced plasma level of creatinine (Crea), blood urea nitrogen (BUN) and pro-inflammation cytokines. Conclusions and Implications: Our investigations provides evidence that NF-κB inhibitor 270 is a potential drug against LPS-induced AKI and ALI in the future.