Dexmedetomidine Protects Against Lipopolysaccharide-Induced Acute Kidney Injury by Enhancing Autophagy Through Inhibition of the PI3K/AKT/mTOR Pathway

Frontiers in Pharmacology
Yuan ZhaoHonggang Fan

Abstract

Acute kidney injury (AKI) is often secondary to sepsis. Previous studies suggest that damaged mitochondria and the inhibition of autophagy results in AKI during sepsis, but dexmedetomidine (DEX) alleviates lipopolysaccharide (LPS)-induced AKI. However, it is uncertain whether the renoprotection of DEX is related to autophagy or the clearance of damaged mitochondria in sepsis-induced AKI. In this study, AKI was induced in rats by injecting 10 mg/kg of LPS intraperitoneally (i.p.). The rats were also pretreated with DEX (30 μg/kg, i.p.) 30 min before the injection of LPS. The structure and function of kidneys harvested from the rats were evaluated, and the protein levels of autophagy-related proteins, oxidative stress levels, and apoptosis levels were measured. Further, atipamezole (Atip) and 3-Methyladenine (3-MA), which are inhibitors of DEX and autophagy, respectively, were administered before the injection of DEX to examine the protective mechanism of DEX. Pretreatment with DEX ameliorated kidney structure and function. DEX decreased the levels of blood urea nitrogen (BUN) and creatinine (Cre), urine kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), reactive oxygen species (ROS), and apoptos...Continue Reading

References

Jun 26, 2002·Kidney International·Won K HanJoseph V Bonventre
Feb 27, 2007·Oncogene·J M Adams, S Cory
Aug 25, 2007·Nature Reviews. Molecular Cell Biology·M Chiara MaiuriGuido Kroemer
Aug 30, 2008·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Davide BolignanoMichele Buemi
Jun 4, 2013·Antioxidants & Redox Signaling·Katherine R Parzych, Daniel J Klionsky
Sep 27, 2014·Cell Death and Differentiation·G FilomeniF Cecconi
Mar 22, 2015·Seminars in Nephrology·Samir M ParikhZheng Dong
Sep 4, 2015·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Yu Ishimoto, Reiko Inagi
Nov 14, 2015·Autophagy·Michael J Munson, Ian G Ganley
Feb 27, 2016·Scientific Reports·Shuqin MeiZheng Dong
Mar 1, 2016·Kidney International·Gur P Kaushal, Sudhir V Shah
Apr 21, 2016·Free Radical Biology & Medicine·Baris Bingol, Morgan Sheng
May 14, 2016·Autophagy·Jeffery HoWilliam K K Wu
Oct 25, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Sheng-Xia WanShuang Ma
Feb 19, 2017·Current Opinion in Genetics & Development·Alexander J Whitworth, Leo J Pallanck
Mar 23, 2017·JAMA : the Journal of the American Medical Association·Yu KawazoeUNKNOWN Dexmedetomidine for Sepsis in Intensive Care Unit Randomized Evaluation (DESIRE) Trial Investigators
Apr 2, 2017·Intensive Care Medicine·Rinaldo BellomoAntoine Schneider
Apr 26, 2017·Autophagy·Tomonori KimuraTamotsu Yoshimori
Dec 7, 2017·Nature·Vincenzo SorrentinoJohan Auwerx
Jun 2, 2018·Circulation·Yuxiao SunQun S Zang
Jul 1, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Kai KangKai-Jiang Yu
Nov 6, 2018·Biosensors & Bioelectronics·Sanni KumarShiv Govind Singh
Feb 13, 2019·Cells·Yuxiao SunQun S Zang
Feb 23, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·You WuZhong-Qiu Lu
Aug 6, 2019·Frontiers in Immunology·Alice AssingerJulie Rayes

❮ Previous
Next ❯

Citations

Aug 18, 2020·Inflammation·Ugur KostakogluHuseyin Avni Uydu
Oct 2, 2020·International Journal of Molecular Sciences·Fang LuoXin Wang
Oct 13, 2020·Molecular Biology Reports·Liangyuan Suo, Mingyu Wang
Nov 28, 2020·International Immunopharmacology·Wenting WangHongsheng Ren
Jun 23, 2021·The Journal of Biological Chemistry·Yafang WangTiffany Horng
Aug 7, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Widuri KhoClaudia D Spies

❮ Previous
Next ❯

Methods Mentioned

BETA
enzyme-linked immunosorbent assay
Assay
light microscopy
PCR
MDA

Software Mentioned

GraphPad Prism
GraphPad

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms