title: Astragaloside IV prevents acute kidney injury in two rodent models by inhibiting oxidative stress and apoptosis pathways.
abstract: Oxidative stress and apoptosis play key role in the pathogenesis of acute kidney injury (AKI). We hypothesize that Astragaloside IV(AS-IV) prevents AKI through inhibiting oxidative stress and apoptosis. The rats were divided into sham control, saline-,vehicle-, or AS-IV-treated groups. AS-IV (20 mg/kg) was orally administered once daily to the rats for 7 consecutive days before terminating the experiments. In ischemia-induced AKI model, experimental rats were subjected to bilateral clamping of the renal arteries for 45 min, followed by reperfusion for 24 h. In contrast-induced AKI model, iopamidol (2.9 g iodine/kg) was administered intravenously into the rats. Renal function, histopathology, oxidative stress and apoptosis were evaluated in these models. Pretreatment with AS-IV significantly decreased blood urea nitrogen, serum creatinine, cystatin C and neutrophil gelatinase-associated lipocalin levels, as well as urinary kidney injury molecule-1 level and tubular injury. AS-IV also reduced oxidative stress and tubular cell apoptosis. The p38 mitogen-activated protein kinase phosphorylation and caspase-3 activity were elevated in kidney tissues from AKI rats, accompanied by an increase in Bax expression and a decrease in Bcl-2 expression at mRNA and protein levels. These changes were prevented by AS-IV pretreatment. Therefore, AS-IV can be developed as a novel therapeutic approach to prevent AKI through targeting inhibition of oxidative stress and apoptosis pathways.
authors: Department of Nephrology and Rheumatology, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China. guidingkun@sina.com.cn
authors: Dingkun
authors: D
authors: Gui
authors: Jianhua
authors: J
authors: Huang
authors: Wei
authors: W
authors: Liu
authors: Yongping
authors: Y
authors: Guo
authors: Wenzhen
authors: W
authors: Xiao
authors: Niansong
authors: N
authors: Wang
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control* / Q000601:surgery; D000209:Acute-Phase Proteins; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000652:urine; D055316:Cystatin C / Q000097:blood; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D007511:Ischemia / Q000601:surgery; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000601:surgery; D007677:Kidney Function Tests; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood; D008297:Male; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000097:blood; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000601:surgery; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D053148:Caspase 3; D015815:Cell Adhesion Molecules; D055316:Cystatin C; D004365:Drugs, Chinese Herbal; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012503:Saponins; D014315:Triterpenes; D048051:p38 Mitogen-Activated Protein Kinases; C110936:Havcr1 protein, rat; C097278:Lcn2 protein, rat; C052064:astragaloside A