title: Antioxidative Stress Effects of Salvia przewalskii Extract in Experimentally Injured Podocytes.
abstract: BACKGROUND
  Oxidative stress is a leading cause of puromycin aminonucleoside (PAN)-induced nephrosis. As the inhibition of oxidative stress may improve injury of podocyte, we aimed at examining the effect of total phenolic acid extract of Salvia przewalskii (SPE) on PAN-induced oxidative stress in vivo and in vitro.
  
  
  METHODS
  Seventy-two male Sprague-Dawley rats were randomly assigned into 6 groups (n = 12), PAN alone, tacrolimus (TAC), SPE (50, 100 and 200 mg/kg) and normal control group. Salvianolic acid B (SalB, 5.52%) and rosmarinic acid (RA, 31.58%) were isolated from SPE. The intensities of 8-oxo-2'-deoxyguanosine (8-OHdG) were evaluated by immunofluorescence. In vitro, the podocytes were assigned into groups of control, PAN alone, TAC (1 μg/ml), SPE (158, 316 μg/ml), SalB (8.5, 17 μg/ml) and RA (25, 50 μg/ml). The intracellular reactive oxygen species (ROS) production and cell apoptosis rate were measured by flow cytometry. Form factor and aspect ratio were calculated to assess mitochondrial morphology.
  
  
  RESULTS
  In vivo, PAN increased the intensity of 8-OHdG in the renal tissue in the PAN group (p < 0.05). The high-dose SPE reduced 8-OHdG significantly at levels comparable to TAC alone (p > 0.05) on day 15. The intracellular ROS production, podocytes apoptosis rate and mitochondrial fragmentation increased significantly following PAN exposure in podocytes (p < 0.05). Treatment with high-dose SalB significantly ameliorated the increase in the expression of ROS and revised the structure of mitochondria. The percentage of apoptotic cells was decreased compared with the PAN group after SPE, SalB, RA, and TAC treatment for 24 h (p < 0.05).
  
  
  CONCLUSIONS
  These findings suggest that high-dose SPE significantly attenuated 8-OHdG in PAN nephrosis. Antioxidative stress effects of high-dose SPE, SalB against PAN-stimulated cultured podocyte via mechanisms include suppression of ROS expression and mitochondria fission. In addition, SPE, SalB and RA can suppress PAN-induced apoptosis.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Jiadai
authors.initials: J
authors.lastname: Xu
authors.forename: Deshu
authors.initials: D
authors.lastname: Dai
authors.forename: Chao
authors.initials: C
authors.lastname: Yan
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Li
authors.forename: Renxian
authors.initials: R
authors.lastname: Tang
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
authors.forename: Hongqi
authors.initials: H
authors.lastname: Ren
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism*; D011692:Puromycin Aminonucleoside / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D027544:Salvia
chemical_list: D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D011692:Puromycin Aminonucleoside; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine