3.8 Compound 270 affects various molecular mechanisms involved
in the pathogenesis of acute kidney and lung injury challenged with
intraperitoneal injection of LPS
NF-κB signaling pathways activated by LPS play vital roles in
inflammation, oxidative stress, endoplasmic reticulum (ER) stress and
autophagy, all these participate in the development of LPS-induced acute
kidney and lung injury (Muriach et
al. , 2014). Myeloperoxidase (MPO) is a specific indicator of
neutrophils and macrophages infiltration and indirectly reflects the
severity of inflammation in injury tissues
(Huang et al. , 2016). Our results
pointed that MPO activity of kidney and lung tissues was higher in the
LPS-treated group compared with the Veh group, and pretreatment with 270
dose dependently reduced mice renal (Figure 8A) and lung (Figure 8E) MPO
activity compared with the LPS group.
Malondialdehyde (MDA) is considered to be a marker reflecting the level
of oxidative stress, and its formation could aggravate damage to cell
membranes (Niu et al. , 2019). The
MDA content of mice in kidney and lung tissues was significantly
increased after 24 h LPS injection, while 270 pretreatment inhibited the
enhancement of MDA content in renal (Figure 8B) and lung (Figure 8F)
tissues induced by LPS. To further elucidate the protective role of 270
in LPS-induced AKI and ALI, the protein levels of ER stress markers (BiP
and CHOP) and autophagy-related factors (LC3A and p62) were measured via
western blotting. Our results showed that LPS obviously promoted the
expression of BiP and CHOP proteins in mice kidney and lung tissues, and
the up-regulation of the BiP and CHOP proteins in kidney (Figure 8C,D)
and lung (Figure 8G,H) tissues was diminished by 270 administration,
indicating that 270 could suppress the activated ER stress. Besides, we
found LPS stimulation elevated the protein levels of LC3A and p62 in
mice kidney and lung tissues, and the effect of LPS on these proteins in
renal (Figure 8C,D) and lung tissues (Figure 8G,H) was normalized by 270
administration, suggesting that 270 could reverse the inhibition effect
of LPS on autophagy.