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International Journal of Biological Macromolecules

International Journal of Biological Macromolecules

IF: 7.7
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Improved bioavailability of polydatin and its protective effect against cisplatin induced nephrotoxicity through self-assembled fucoidan and carboxymethyl chitosan?…

Published:9 December 2024 DOI: 10.1016/j.ijbiomac.2024.138577 PMID: 39657878
Yinghan Wang,?Pengyu Xue,?Liang Gao,?Xuefei Wang,?Shilin Zhou,?Xiaochen Wu,?Chuanlong Guo

Abstract

Cisplatin induced acute kidney injury (AKI) is clinically prevalent, with a complex pathogenesis and a lack of effective therapeutic drugs. Polydatin (Po) has excellent biological activity, but its low solubility and bioavailability limit its application. In this study, fucoidan (Fu) and carboxymethyl chitosan (Cs) self-assembled into nanoparticles through electrostatic interactions/hydrogen bonding and loaded Po (Fu/Cs Po NPs). In vitro studies found that Fu/Cs Po NPs protected human renal tubular epithelial (HK-2) cells from cisplatin induced damage and accumulation of reactive oxygen species (ROS). Mechanistic studies showed that Fu/Cs Po NPs inhibited cisplatin induced DNA damage and activation of cyclic guanosine monophosphate synthase (cGAS) and intron gene stimulator (STING) pathways. In vivo studies showed that Fu/Cs Po NPs treatment alleviated cisplatin induced AKI symptoms, including elevated blood urea nitrogen (BUN) and serum creatinine (SCr), as well as pathological damage to kidney tissues. In vivo mechanism studies also showed that Fu/Cs Po NPs treatment inhibited cisplatin induced DNA damage and activation of the cGAS-STING pathway. The pharmacokinetic and tissue distribution results demonstrated that the Fu/Cs delivery system enhanced the bioavailability and kidney accumulation of Po in vivo. In summary, our study provided potential drugs for the treatment of cisplatin induced AKI.

Substances (3)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Thiazolyl Blue 298-93-1 C18H16BrN5S 401 suppliers $7.00-$1596.00
Hoechst 33258 23491-45-4 C25H25ClN6O 228 suppliers $33.90-$1432.00
2′,7′-Dichlorodihydrofluorescein Diacetate 4091-99-0 C24H16Cl2O7 178 suppliers $33.00-$1947.00

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