دورية أكاديمية

Control release of mitochondria-targeted antioxidant by injectable self-assembling peptide hydrogel ameliorated persistent mitochondrial dysfunction and inflammation after acute kidney injury.

التفاصيل البيبلوغرافية
العنوان: Control release of mitochondria-targeted antioxidant by injectable self-assembling peptide hydrogel ameliorated persistent mitochondrial dysfunction and inflammation after acute kidney injury.
المؤلفون: Zhao, Meng, Zhou, Yijie, Liu, Shuyun, Li, Lan, Chen, Younan, Cheng, Jingqiu, Lu, Yanrong, Liu, Jingping
المصدر: Drug Delivery; Nov2018, Vol. 25 Issue 1, p546-554, 9p
مصطلحات موضوعية: ACUTE kidney failure, MITOCHONDRIA, REPERFUSION injury, MITOCHONDRIAL DNA, OXIDATIVE stress
مستخلص: Persistent mitochondrial injury occurs after acute kidney injury (AKI) and mitochondria-targeted antioxidant Mito-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) (MT) has shown benefits for AKI, but its efficiency is limited by short half-life and side effect in vivo. Self-assembling peptide (SAP) hydrogel is a robust platform for drug delivery. This study aims to develop an SAP-based carrier to slow release MT for enhancing its long-term therapeutic potency on AKI. The KLD with aspartic acid (KLDD) was designed. The microstructure and in vitro release of MT was assayed. The protective role of MT-loaded SAP (SAP-MT) hydrogel on renal mitochondrial injury, tubular apoptosis, and inflammation was evaluated in mice at five days after ischemia-reperfusion injury (IRI). Our results showed that KLDD could self-assemble into cross-linked nanofiber hydrogel and it had lower release rate than free MT and KLD hydrogel. Compared to IRI and free MT mice, SAP-MT mice exerted reduced renal mitochondria-produced ROS (mtROS) and improved mitochondrial biogenesis and architecture. Consequently, SAP-MT mice showed less renal tubular cell apoptosis, kidney injury marker kidney injury molecule-1 (Kim-1) expression, lower level of pro-inflammatory factors expression, and macrophages infiltration than those of IRI and free MT mice. This study suggested that SAP-MT ameliorated IRI due to its extended mitochondrial protection role than free MT and thus improved the long-term outcomes of AKI. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:10717544
DOI:10.1080/10717544.2018.1440445