title: Preclinical efficacy of Dexmedetomidine on spinal cord injury provoked oxidative renal damage.
abstract: OBJECTIVE
  Oxidative renal injury is the mainstay in patients with spinal cord injury (SCI) and it may eventuate to chronic renal failure. In our study, we investigated the potential of α2-adrenoreceptor agonist Dexmedetomidine (Dex) in ameliorating SCI provoked oxidative renal assault.
  
  
  METHODS
  Complete SCI was generated by surgical transaction of the cord at the T10-12 level. Dex administration (50 mcg/kg, b.wt, intraperitoneally) was initiated 12 h after the surgery for 10 days. Then, blood was collected and kidneys were removed to evaluate the efficacy of Dex on post-SCI renal complications.
  
  
  RESULTS
  Dex treatment significantly attenuated elevated serum creatinine and blood urea nitrogen in SCI rats to normalcy. Further in SCI rats elevated level of MDA, protein carbonyl and myeloperoxidase (MPO) were observed and Dex treatment significantly attenuated these toxic manifestations to normalcy. Besides in SCI rats, the antioxidants (SOD, CAT, Gpx and GST and GSH) levels were significantly diminished and Dex treated rats significantly restored the antioxidants level in renal tissue to normalcy. Notably, in our study the protein expression of inflammatory cytokines (TNF-α and IL-6) and cleaved caspase-3 were upregulated in renal tissue of SCI rats. Fascinatingly, Dex treatment downregulated the protein expression of TNF-α, IL-6 and cleaved caspase-3 by anti-inflammatory, antiapoptotic mechanism. Furthermore, SCI rats displayed upregulated protein expression of kidney of SCI rats. Dex treatment diminished the renal apoptosis by downregulating the cleaved caspase-3 expression.
  
  
  CONCLUSIONS
  Taken together, these results accentuate that Dex may be a beneficial clinical agent to combat post-SCI renal complications.
authors.affiliation: a Department of Anesthesiology , The Affiliated Hospital of Qingdao University Medical College , Qingdao , P.R. China .
authors.forename: Wang
authors.initials: W
authors.lastname: Shou-Shi
authors.affiliation: b Department of Oncology , Qingdao Central Hospital , Qingdao , P.R. China , and.
authors.forename: Song
authors.initials: S
authors.lastname: Ting-Ting
authors.affiliation: c Department of Anesthesiology , Qingdao Central Hospital , Qingdao , P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ji-Shun
authors.affiliation: a Department of Anesthesiology , The Affiliated Hospital of Qingdao University Medical College , Qingdao , P.R. China .
authors.forename: Chu
authors.initials: C
authors.lastname: Hai-Chen
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D020927:Dexmedetomidine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D011183:Postoperative Complications / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000601:surgery*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D020927:Dexmedetomidine; D003404:Creatinine; D009195:Peroxidase; D053148:Caspase 3
keywords: Dexmedetomidine; inflammation; oxidative stress; renal damage; spinal cord injury