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.