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

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-1α (HNF-1α) 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.PMID:37885225 | DOI:10.1080/00498254.2023.2270046
Source: Xenobiotica - Category: Research Authors: Source Type: research