1. Arctigenin: A two-edged sword in ischemia/reperfusion induced acute kidney injury.
- Author
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Han F, Xia XX, Dou M, Wang YX, Xue WJ, Ding XM, Zheng J, Ding CG, and Tian PX
- Subjects
- Acute Kidney Injury etiology, Acute Kidney Injury pathology, Animals, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents adverse effects, Disease Models, Animal, Dose-Response Relationship, Drug, Furans administration & dosage, Furans adverse effects, Inflammation, Kidney immunology, Kidney metabolism, Kidney pathology, Lignans administration & dosage, Lignans adverse effects, Male, Mice, Inbred C57BL, Oxidative Stress drug effects, Reperfusion Injury complications, Reperfusion Injury pathology, Acute Kidney Injury prevention & control, Anti-Inflammatory Agents therapeutic use, Apoptosis drug effects, Furans therapeutic use, Kidney drug effects, Lignans therapeutic use, Reperfusion Injury drug therapy
- Abstract
Arctigenin (ATG) is one of the main active substances in fruit derived from Arctium lappa L. Previous studies have reported that ATG have antitumor, neuroprotective, antioxidant, antifibrosis and anti-inflammatory functions. However, the actions of ATG in kidney with acute injury following ischemia/ reperfusion (I/R) is still uncertain. In our study, mice were subjected to kidney I/R by having the kidney pedicles clamped and administered with vehicle or ATG (1, 3 or 9 mg/kg/d) via oral gavage for 7 consecutive days prior to I/R. Notably, ATG aggravated kidney I/R injury with the concentration increases. Multiple biochemical assays and histological examination showed ATG significantly alleviated the inflammatory response as reflected by a decreased expression of proinflammatory cytokine, TLR4/MyD88, and NF-κB, along with the infiltration of CD68
+ macrophage and CD11b+ Gr1+ neutrophil in the kidneys. Meanwhile, ATG alleviated I/R-induced oxidative stress proved by increasing kidney manganese superoxide dismutase and glutathione peroxidase activity but reducing levels of malonaldehyde and inducible nitric oxide synthase. On the contrary, apoptosis was significantly increased in kidneys of ATG-treated mice compared with vehicle-treated controls, especially in tubular cells. There were increased numbers of TUNEL positive cells and increased Bcl-2, Bax, cleaved-caspase-3, and cleaved-caspase-9 expression. The current study demonstrates that pretreatment of ATG aggravates I/R induced acute kidney injury by increasing apoptosis of tubular cells despite reducing infiltrating inflammatory cells and proinflammatory cytokine., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)- Published
- 2018
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