Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice

Abstract

Lipopolysaccharide (LPS) is an endotoxin that plays a crucial role in septic acute kidney injury (AKI). Hispidulin is a natural flavonoid that possesses various biological activities. Recent studies have shown that hispidulin administration alleviates various inflammatory diseases in animal models. This study aimed to investigate the renoprotective effect of hispidulin on LPS-induced AKI. Male C57BL/6 mice were administered LPS (10 mg/kg) with or without hispidulin (50 mg/kg). Hispidulin administration attenuated renal dysfunction, histological alterations, and the upregulation of neutrophil gelatinase-associated lipocalin. This flavonoid also reduced cytokine production and Toll-like receptor 4 expression, inhibited nuclear factor-κB and mitogen-activated protein kinase cascades, and alleviated immune cell infiltration. The oxidation of lipids and DNA was also inhibited by hispidulin administration. This antioxidant effect of hispidulin was associated with the downregulation of NADPH oxidase 4, the activation of catalase and superoxide dismutase activities, and the restoration of glutathione levels. Moreover, hispidulin administration attenuated tubular cell apoptosis by inhibiting caspase-3 pathway. These data suggest that hispidulin ameliorates endotoxin-induced kidney injury by suppressing inflammation, oxidative stress, and tubular cell death.

Protective Effects of Carnosol on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

“…Renal amount of the lipid peroxidation product MDA [ 34 , 35 ] was also reduced by CS (UUO, 6.3 ± 0.6 nmol/mg protein vs. UUO+CS, 3.1 ± 0.4 nmol/mg protein, p < 0.001) ( Figure 5 C). In addition, IF staining for 8-OHdG, an oxidative nucleoside product [ 36 ], revealed that the number of 8-OHdG-positive cells increased after UUO surgery (Sham, 1.1 ± 0.4 vs. UUO, 40.3 ± 4.4, p < 0.001) ( Figure 5 D,E). However, CS treatment remarkably reduced the number of 8-OHdG-positive cells (UUO, 40.3 ± 4.4 vs. UUO+CS, 6.4 ± 1.3, p < 0.001) ( Figure 5 D,E).…”

Protective Effects of Orexin A in a Murine Model of Cisplatin-Induced Acute Kidney Injury

“…Renal levels of MDA, another lipid peroxidation product [ 29 ], were also reduced by OXA (CP, 4.5 ± 0.5 nmol/mg protein vs. CP + OXA, 1.8 ± 0.3 nmol/mg protein, p < 0.001) ( Figure 4 C). In addition, OXA reduced renal levels of 8-OHdG, a product of oxidative DNA damage [ 30 ] (CP, 92.6 ± 9.6 ng/g protein vs. CP + OXA, 65.9 ± 6.5 ng/g protein, p < 0.05) ( Figure 4 D). OXA also increased GSH levels (CP, 2.1 ± 0.3 nmol/mg protein vs. CP + OXA, 3.0 ± 0.2 nmol/mg protein, p < 0.01) and GSH/GSSG ratio (CP, 1.1 ± 0.2 vs. CP + OXA, 2.6 ± 0.2, p < 0.001), while decreasing GSSG levels (CP, 1.8 ± 0.2 nmol/mg protein vs. CP + OXA, 1.2 ± 0.2 nmol/mg protein, p < 0.05) ( Figure 4 E–G).…”

Study of hispidulin in the treatment of uric acid nephropathy based on NF‐κB signaling pathway

“…HE‐staining results showed that hispidulin could alleviate renal pathological injury, renal interstitial fibrosis, and inflammatory infiltration in UAN rats. Consistently, in LPS‐induced acute kidney injury mice, hispidulin is determined to ameliorate endotoxin‐induced kidney injury by suppressing inflammation, oxidative stress, and tubular cell death (Kim & Leem, 2022). In addition, hispidulin is also reported to relieve high‐glucose‐induced podocyte injury by regulating protective autophagy (Wu et al., 2018).…”