title: Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats.
abstract: BACKGROUND
  Sulodexide is a powerful antithrombin agent with reno-protective property. However, whether it has beneficial effects on Contrast-Induced Nephropathy (CIN) remained elusive. In the current study, we evaluated the therapeutic effects of Sulodexide on CIN and investigated the potential mechanisms.
  
  
  METHODS
  CIN model was induced by intravenous injection of indomethacin, followed by Ioversol and L-NAME. Sprague-Dawley rats were divided into 4 groups: control group, CIN group, CIN+vehicle group (CIN rats pretreated with vehicle) and CIN+ Sulodexide (CIN rats pretreated with Sulodexide). Sulodexide or an equivalent volume of vehicle was intravenously delivered 30 min before the induction of CIN. All the animals were sacrificed at 24h after CIN and tissues were harvested to evaluate renal injury, kidney oxidative stress and apoptosis levels. Plasma antithrombin III (ATIII) activities were also measured.
  
  
  RESULTS
  Compared to the untreated CIN group, improved renal function, reduced tubular injury, decreased levels of oxidative stress and apoptosis were observed in CIN rats receiving Sulodexide injection. In addition, we also found that ATIII activity was significantly higher in Sulodexide-administered group than that in vehicle-injected CIN rats. For in vitro studies, HK2 cells were exposed to Ioversol and the cyto-protective effects of Sulodexide were also determined. Sulodexide pretreatment protected HK2 cells against the cytotoxicity of Ioversol via inhibiting caspase-3 activity. Preincubation with Sulodexide could also attenuate H2O2-induced increases in ROS, apoptosis and caspase-3 levels.
  
  
  CONCLUSIONS
  Taken together, Sulodexide could protect against CIN through activating ATIII, and inhibiting oxidative stress, inflammation and apoptosis.
authors.affiliation: Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.forename: Jianyong
authors.initials: J
authors.lastname: Yin
authors.forename: Zeyuan
authors.initials: Z
authors.lastname: Lu
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Kong
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Zhang
authors.forename: Binghui
authors.initials: B
authors.lastname: Zhao
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D003287:Contrast Media / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D006025:Glycosaminoglycans / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007249:Inflammation / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D014283:Triiodobenzoic Acids
chemical_list: D003287:Contrast Media; D006025:Glycosaminoglycans; D020011:Protective Agents; D014283:Triiodobenzoic Acids; C007858:glucuronyl glucosamine glycan sulfate; D000990:Antithrombin III; D003404:Creatinine; D006861:Hydrogen Peroxide; D053148:Caspase 3; C054871:ioversol