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• W2897984810 abstract "Reactive oxygen species (ROS) overproduction and renal tubular epithelial cell (TEC) apoptosis are key mechanisms of contrast-induced acute kidney injury (CI-AKI). Mitochondria are the main source of intracellular ROS. In the present study, the characteristics of mitophagy and the effects of rapamycin on contrast-induced abnormalities in oxidative stress, mitochondrial injury and mitophagy, TEC apoptosis and renal function were investigated in a CI-AKI rat model. Rats were divided into control group, CI-AKI group, and pretreatment groups (with rapamycin dose of 2 or 5 mg/kg). CI-AKI was induced by intraperitoneal injection of iohexol (12.25 g iodine/kg). Renal malondialdehyde (MDA) and catalase (CAT) were measured as oxidative markers. Light-chain 3 (LC3), P62, Beclin-1, PTEN-induced putative kinase (Pink1), and cytochrome c (Cyt c) expression were measured by Western blot. Mitochondrial membrane potential (ΔΨm) was determined by JC-1, colocalization of LC3-labeled autophagosomes with TOMM20-labeled mitochondria or LAMP2-labeled lysosomes was observed by fluorescence microscopy. Significantly increased serum creatinine (Scr), MDA and CAT, obvious mitochondrial injury including increase in cytosolic/mitochondrial Cyt c and decrease in ΔΨm, TEC apoptosis were induced by contrast administration. Contrast administration induced an increased expression of LC3II/I, Beclin-1, and Pink1 and decreased expression of P62. Rapamycin pretreatment induced overexpression of LC3II/I and Beclin-1. Moreover, LC3-labeled autophagosomes increasingly overlapped with TOMM20-labeled mitochondria and LAMP2-labeled lysosomes in CI-AKI, which was further enhanced by rapamycin administration. Contrast-induced Scr increase, oxidative stress, mitochondrial injury, TEC apoptosis, and necrosis were dose-dependently attenuated by rapamycin pretreatment. Rapamycin exerts renoprotective effects against CI-AKI by attenuating mitochondrial injury and oxidative stress, which might be associated with increasing mitophagy." @default.
• W2897984810 created "2018-10-26" @default.
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• W2897984810 date "2018-11-21" @default.
• W2897984810 modified "2023-09-25" @default.
• W2897984810 title "Rapamycin attenuates mitochondrial injury and renal tubular cell apoptosis in experimental contrast-induced acute kidney injury in rats" @default.
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• W2897984810 doi "https://doi.org/10.1042/bsr20180876" @default.
• W2897984810 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6246763" @default.
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