Wang, Lei; Li, Zhong-Yao; Zhong, Chong-Lei; Teng, Zi-Yang; Wang, Bin; Rehman, Asma; Han, Li-Wen; Zeng, Ke-Wu; Zhang, Ji-Guo; Lu, Zhi-Yuan

DOI: PMID:

Abstract

Background: Sepsis is a life-threatening infectious disease characterized by an uncontrolled infammatory response and consequent multi-organ dysfunction. The kidneys, as primary excretory organs with high blood fow, are particularly susceptible to damage during sepsis. Nonetheless, the existing treatment options for sepsis-associated acute kidney injury (SA-AKI) are still restricted. Nanomedicine, especially carbon dots (CDs), has attracted considerable interest lately for outstanding biomedical characteristics. Methods: To avoid the generation of toxic efects, the natural CDs derived from Ziziphi Spinosae Semen (Z-CDs) were synthesized employing a hydrothermal method. The free radical scavenging capabilities of Z-CDs were evaluated by utilizing ABTS assay, NBT method, and Fenton reaction. A lipopolysaccharide (LPS)-stimulated RAW 264.7 cell model was used to explore the therapeutic potential of Z-CDs on cellular oxidative stress and infammation. The CuSO4-induced zebrafsh infammation model and LPS-exposed SA-AKI mouse model were employed to assess the therapeutic efcacy of Z-CDs in vivo. Results: The synthesized Z-CDs exhibited distinctive unsaturated surface functional groups, which confer exceptional biocompatibility and the ability to scavenge free radicals. Moreover, Z-CDs were particularly efective in eliminating excess reactive oxygen species (ROS) in cells, thus protecting mitochondrial function from oxidative damage. Notably, Z-CDs have demonstrated signifcant therapeutic benefts in protecting kidney tissue in SA-AKI mouse model with minimizing side efects. In mechanism, Z-CDs efectively reduced ROS production, thereby alleviating infammatory responses in macrophages through the suppression of the NF-κB pathway. Conclusions: This study developed a multifunctional nanomedicine derived from traditional medicinal herb, providing a promising pathway for the advancement of innovative drug therapies to treat SA-AKI.

Keywords

Sepsis ; Acute kidney injury ; Carbon dots ; Phytochemicals ; Antioxidant ; NF-κB pathway

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