Protective effect of taraxasterol on ischemia/reperfusion-induced acute kidney injury via inhibition of oxidative stress, inflammation, and apoptosis
| Autor: | Yun Xie, Chuanlei Li, Nan Zhu, Jun Liu, Qing Yu, Jinfang Bao, Zhihuang Zheng, Zhigang Zhou |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Necrosis Cell Survival Immunology Inflammation Apoptosis Pharmacology medicine.disease_cause Proinflammatory cytokine Cell Line 03 medical and health sciences Mice 0302 clinical medicine medicine Immunology and Allergy Animals Humans chemistry.chemical_classification Kidney Reactive oxygen species biology Acute Kidney Injury medicine.disease Triterpenes Mice Inbred C57BL Oxidative Stress Sterols 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Myeloperoxidase Reperfusion Injury biology.protein medicine.symptom Reperfusion injury Oxidative stress |
| Zdroj: | International immunopharmacology. 89 |
| ISSN: | 1878-1705 |
| Popis: | Ischemia/reperfusion injury (IRI), the most common cause of acute kidney injury (AKI), is correlated with oxidative stress and subsequent inflammation. Taraxasterol, a natural product, has been shown to exert anti-oxidative and anti-inflammatory effects. However, the role of taraxasterol in renal IRI remains unknown. In this study, mice were subjected to 30 min of bilateral renal ischemia-reperfusion to induce AKI. Cellular hypoxia/reoxygenation (H/R) was used to mimic IRI in vitro. Western blotting, immunochemistry, immunofluorescence, TUNEL staining, ELISA, and flow cytometry were performed to evaluate kidney damage, oxidative stress, inflammation, and apoptosis in vivo and in vitro. Treatment with taraxasterol attenuated the following in a dose-dependent manner: tubular damage; infiltration of F4/80-positive macrophages; renal interstitial fibrosis; myeloperoxidase (MPO) activity; and expression of the inflammatory cytokines tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1). Moreover, taraxasterol treatment remarkably ameliorated apoptosis in the kidney by decreasing Bax expression and conserving Bcl2. Notably, MitoSOX assay revealed that treatment with taraxasterol suppressed the production of mitochondrial reactive oxygen species. Furthermore, taraxasterol suppressed phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) of the mitogen-activated protein kinase (MAPK) signaling pathways in vivo and in vitro. In conclusion, these findings indicate that taraxasterol has a protective effect on IRI-induced AKI via inhibition of oxidative stress, inflammation, and apoptosis. |
| Databáze: | OpenAIRE |
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