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

Abstract

1. 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.

2. The model of cisplatin-induced AKI was established, and hyperoside was preadministered to investigate its effect on improving kidney injury.

3. 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-1α (HNF-1α) and pregnane X receptor (PXR).

4. 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.

Keywords:

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

Acknowledgments

We thank Dr. Yi Zheng from Shandong University for providing plasmids.

Disclosure statement

The authors declare that there are no conflicts of interest.

Data availability statement

The raw/processed data required to reproduce these findings cannot be shared at this time as the data also forms part of an ongoing study.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (82174072 and 81673684), ‘Double First-Class’ University Projects (CPU2018GY33), and The Open Project Program of the MOE Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University) (No. DQCP20/21MS05).