title: Potential nephroprotective effects of the Chinese herb Angelica sinensis against cisplatin tubulotoxicity.
abstract: BACKGROUND
  Acute kidney injury (AKI) is often encountered in patients receiving cisplatin (CisPt), a chemotherapeutic drug that induces numerous toxic side effects. Techniques used to limit nephrotoxicity during CisPt treatment are not fully effective; about a third of patients experience AKI. New nephroprotective strategies, including pharmacological approaches, must be developed.
  
  
  OBJECTIVE
  The present study investigated the nephroprotective potential of Angelica sinensis (Oliv.) Diels (Apiaceae) root towards CisPt tubulotoxicity.
  
  
  METHODS
  HK-2 cells were incubated with CisPt (10 µM) and/or with a methanolic extract of A. sinensis (AS). Nephroprotective capacity was evaluated by means of cellular viability (resazurin assay) and apoptosis (annexin-V/PI staining), oxidative stress generation (H2DCF-DA oxidation), Ki-67 index (immunofluorescence), cell cycle analysis (DNA staining), cell migration rate (scratch assay), extracellular matrix deposition (collagen determination), and β-catenin relocalization.
  
  
  RESULTS
  CisPt decreased cell viability [76% versus Ctrl], which was associated with an increased apoptosis. Simultaneous treatment with 50 µg/ml AS enhanced cell survival [84% versus Ctrl] and decreased the apoptosis rate. AS could not alleviate CisPt-induced oxidative stress; but doses of 5 and 50 µg/ml raised the Ki-67 index [135 and 244% versus Ctrl] and cell migration rates [1.2 and 1.3-fold versus Ctrl]. Finally, both doses of AS limited the amount of collagen deposition [121.6 and 119.6% for 5 and 50 µg/ml, respectively, versus 131.0% for CisPt-treated cells] and prevented the relocalization of β-catenin from the membrane to the nucleus.
  
  
  CONCLUSIONS
  These results confirm the nephroprotective potential of A. sinensis and require further investigations aiming at identifying its active compounds.
authors.affiliation: Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles (ULB) , Brussels , Belgium .
authors.forename: Valérian
authors.initials: V
authors.lastname: Bunel
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Antoine
authors.forename: Joëlle
authors.initials: J
authors.lastname: Nortier
authors.forename: Pierre
authors.initials: P
authors.lastname: Duez
authors.forename: Caroline
authors.initials: C
authors.lastname: Stévigny
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D029971:Angelica sinensis; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000633:toxicity*; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D018517:Plant Roots; D020011:Protective Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D004365:Drugs, Chinese Herbal; D020011:Protective Agents; D002945:Cisplatin
keywords: HK-2 cells; Ki-67; apoptosis; collagen; nephroprotection; oxidative stress; regeneration; β-Catenin