Prevention of LPS-Induced Acute Kidney Injury in Mice by Bavachin and Its Potential Mechanisms

Abstract

Acute kidney injury (AKI) is a serious complication of sepsis with a rapid onset and high mortality rate. Bavachin, an active component of Psoralea corylifolia L., reportedly has antioxidant, anti-apoptotic, and anti-inflammatory effects; however, its beneficial effects on AKI remain undetermined. We investigated the protective effect of bavachin on lipopolysaccharide (LPS)-induced AKI in mice and elucidated the underlying mechanism in human renal tubular epithelial HK-2 cells. Increased serum creatinine and blood urea nitrogen levels were observed in LPS-injected mice; however, bavachin pretreatment significantly inhibited this increase. Bavachin improved the kidney injury score and decreased the expression level of tubular injury markers, such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), in both LPS-injected mice and LPS-treated HK-2 cells. LPS-induced oxidative stress via phosphorylated protein kinase C (PKC) β and upregulation of the NADPH oxidase (NOX) 4 pathway was also significantly decreased by treatment with bavachin. Moreover, bavachin treatment inhibited the phosphorylation of MAPKs (P38, ERK, and JNK) and nuclear factor (NF)-κB, as well as the increase in inflammatory cytokine levels in LPS-injected mice. Krüppel-like factor 5 (KLF5) expression was upregulated in the LPS-treated HK-2 cells and kidneys of LPS-injected mice. However, RNAi-mediated silencing of KLF5 inhibited the phosphorylation of NF-kB, consequently reversing LPS-induced KIM-1 and NGAL expression in HK-2 cells. Therefore, bavachin may ameliorate LPS-induced AKI by inhibiting oxidative stress and inflammation via the downregulation of the PKCβ/MAPK/KLF5 axis.

Eupatilin Ameliorates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting Inflammation, Oxidative Stress, and Apoptosis in Mice

“…To investigate the mechanism underlying the anti-inflammatory effect of EUP, we examined MAPK and NF-κB signaling cascades in the kidney. These pathways are known to play an important role in inflammatory responses [ 34 , 35 , 36 ]. We found that EUP significantly inhibited activation of MAPK and NF-κB cascades.…”

“…However, EUP significantly inhibited macrophage infiltration (Figure 4C,D). Mitogen-activated protein kinase (MAPK) and NF-κB signaling cascades play key roles in the inflammatory response of septic AKI [34][35][36]. Therefore, we next investigated the action of EUP on MAPK and NF-κB pathways in LPS-treated mice.…”

Protective effect of citronellol in rhabdomyolysis-induced acute kidney injury in mice

“…All mice were euthanized 24hrs after glycerol injection by diethyl ether followed by cervical dislocation [ 8 ]. The right kidneys were extracted and homogenized [ 9 , 10 ] and kept frozen for later measurement of myoglobin, cleaved caspase-3, and BAX using ELISA (MY BioSource, USA). The left kidneys were fixed in formalin for histopathological analysis using hematoxylin and eosin (H&E) staining [ 9 , 10 ].…”

Acetyl-CoA synthetase 2 induces pyroptosis and inflammation of renal epithelial tubular cells in sepsis-induced acute kidney injury by upregulating the KLF5/NF-κB pathway

“…We were particularly interested in the differential expression of the gene encoding the transcription factor Krüppel Like Factor 5 (KLF5), which was recently identified to be overexpressed in RTECs of the septic AKI model [21]. In addition, this transcription factor has been reported to mediate the activity of activated NF-κB [22,23]. We further explored the possibility that ACSS2 regulates NLRP3 activation and pyroptosis by influencing the expression of KLF5.…”