title: Valsartan Protects Against Contrast-Induced Acute Kidney Injury in Rats by Inhibiting Endoplasmic Reticulum Stress-Induced Apoptosis.
abstract: Contrast-induced acute kidney injury (CI-AKI) is a serious complication of the administration of iodinated contrast media (CM) for diagnostic and interventional cardiovascular procedures and is associated with substantial morbidity and mortality. While the preventative measures can mitigate the risk of CI-AKI, there remains a need for novel and effective therapeutic approaches. The pathogenesis of CI-AKI is complex and not completely understood. CM-induced renal tubular cell apoptosis caused by the activation of endoplasmic reticulum (ER) stress is involved in CIAKI. We previously demonstrated that valsartan alleviated CM-induced human renal tubular cell apoptosis by inhibiting ER stress in vitro. However, the nephroprotective effect of valsartan on CI-AKI in vivo has not been investigated. Therefore, the aim of this study was to explore the protective effect of valsartan in a rat model of CI-AKI by measuring the amelioration of renal damage and the changes in ER stressrelated biomarkers.
  
  
  
  Our results showed that the radiocontrast agent meglumine diatrizoate caused significant renal insufficiency, renin-angiotensin system (RAS) activation, and renal tubular apoptosis by triggering ER stress through activation of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), caspase 12, CCAAT/enhancer-binding protein-homologous protein (CHOP) and c-Jun N-terminal protein kinase (JNK) (P<0.05; n=6 in each group). Pre-treatment with valsartan significantly alleviated renal dysfunction, pathological injury, and apoptosis along with the inhibition of ER stressrelated biomarkers (P<0.05; n=8 in each group).
  
  
  
  Valsartan could protect against meglumine diatrizoate-induced kidney injury in rats by inhibiting the ER stress-induced apoptosis, making it a promising strategy for preventing CI-AKI.
authors: Yan
authors: Y
authors: Sun
authors: Ping-An
authors: PA
authors: Peng
authors: Yue
authors: Y
authors: Ma
authors: Xiao-Li
authors: XL
authors: Liu
authors: Yi
authors: Y
authors: Yu
authors: Shuo
authors: S
authors: Jia
authors: Xiao-Han
authors: XH
authors: Xu
authors: Si-Jing
authors: SJ
authors: Wu
authors: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China.
authors: Yu-Jie
authors: YJ
authors: Zhou
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053454:Caspase 12 / Q000378:metabolism; D003287:Contrast Media; D019610:Cytoprotection; D003974:Diatrizoate Meglumine; D004195:Disease Models, Animal; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000378:metabolism; D000068756:Valsartan / Q000494:pharmacology*
chemical_list: C497110:Atf4 protein, rat; D003287:Contrast Media; C497251:Ddit3 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C051684:GRP78 protein, rat; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP; D003974:Diatrizoate Meglumine; D000068756:Valsartan; D048031:JNK Mitogen-Activated Protein Kinases; C506443:Casp12 protein, rat; D053454:Caspase 12
keywords: Contrast-induced acute kidney injury; apoptosis; endoplasmic reticulum stress; valsartan
  