Hyperoside ameliorates cisplatin-induced acute kidney injury by regulating the expression and function of Oat1

作者：Yuan, Wenjing; Kou, Shanshan; Ma, Ying; Qian, Yusi; Li, Xinyu; Chai, Yuanyuan; Jiang, Zhenzhou; Zhang, Luyong; Sun, Lixin; Huang, Xin^*

来源：Xenobiotica; the fate of foreign compounds in biological systems, 2023, 53(8-9): 559-571.

DOI：10.1080/00498254.2023.2270046

• Hyperoside
• cisplatin
• acute kidney injury
• Oat1
• indoxyl sulphate

Cisplatin is a widely used chemotherapeutic agent to treat solid tumours in clinics. However, cisplatin-induced acute kidney injury (AKI) limits its clinical application. This study investigated the effect of hyperoside (a flavonol glycoside compound) on regulating AKI.The model of cisplatin-induced AKI was established, and hyperoside was preadministered to investigate its effect on improving kidney injury.Hyperoside ameliorated renal pathological damage, reduced the accumulation of SCr, BUN, Kim-1 and indoxyl sulphate in vivo, increased the excretion of indoxyl sulphate into the urine, and upregulated the expression of renal organic anion transporter 1 (Oat1). Moreover, evaluation of rat kidney slices demonstrated that hyperoside promoted the uptake of PAH (p-aminohippurate, the Oat1 substrate), which was confirmed by transient over-expression of OAT1 in HEK-293T cells. Additionally, hyperoside upregulated the mRNA expression of Oat1 upstream regulators hepatocyte nuclear factor-1 alpha (HNF-1 alpha) and pregnane X receptor (PXR).These findings indicated hyperoside could protect against cisplatin-induced AKI by promoting indoxyl sulphate excretion through regulating the expression and function of Oat1, suggesting hyperoside may offer a potential tactic for cisplatin-induced AKI treatment.

• 单位
  广东药学院