title: Dexmedetomidine protects against cisplatin-induced acute kidney injury in mice through regulating apoptosis and inflammation.
abstract: OBJECTIVE
  Cisplatin-based chemotherapy has been widely used in the perioperative period of cancer surgery, which exacerbates the risk of renal injury. In this study, we examined whether dexmedetomidine (DEX), a commonly used anesthetic adjuvant, shows a protective effect against cisplatin-induced acute kidney injury.
  
  
  METHODS
  Acute kidney injury in mice was induced by cisplatin.
  
  
  METHODS
  Mice were administered with DEX 25 μg/kg or atipamezole 250 μg/kg (once a day, for 3 days) after cisplatin treatment.
  
  
  METHODS
  The renal function and tubular damage score were evaluated at 72 h following cisplatin administration. Apoptotic tubular cells were detected by TUNEL assay. Caspase-3, p53, Bax, F4/80+macrophages, CD3+T cells, and NF-κB were examined by immunohistochemistry staining or Western blot. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1 in kidney were measured using real-time polymerase chain reaction.
  
  
  RESULTS
  DEX treatment preserved renal function and reduced tubular damage score of mice after cisplatin administration. Mice treated with DEX exhibited less apoptotic tubular cells in response to cisplatin insult, which was associated with decreased Bax and reduced activation of p53 and caspase-3. DEX suppressed the infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was involved in the inhibition of NF-κB activation and decreased expression of TNF-α, IL-1β, IL-6, and MCP-1. Furthermore, we showed that the renoprotective effect conferred by DEX may be related to α2adrenoceptor-dependent pathway.
  
  
  CONCLUSIONS
  We demonstrate that DEX protects the kidney against cisplatin-induced AKI by the regulation of apoptosis and inflammatory response.
authors.affiliation: Department of Anesthesiology, Affiliated Foshan Hospital of SUN YAT-SEN University, Foshan, 528000, China.
authors.forename: H
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Anesthesiology, Affiliated Foshan Hospital of SUN YAT-SEN University, Foshan, 528000, China.
authors.forename: H-Z
authors.initials: HZ
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Affiliated Foshan Hospital of SUN YAT-SEN University, Foshan, 528000, China.
authors.forename: H-B
authors.initials: HB
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Affiliated Foshan Hospital of SUN YAT-SEN University, Foshan, 528000, China.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Zhong
authors.affiliation: Department of Anesthesiology, Affiliated Foshan Hospital of SUN YAT-SEN University, Foshan, 528000, China.
authors.forename: C-X
authors.initials: CX
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Affiliated Foshan Hospital of SUN YAT-SEN University, Foshan, 528000, China. foshanzhangbin@126.com.
authors.forename: B
authors.initials: B
authors.lastname: Zhang
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D002945:Cisplatin; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000235:genetics; D020927:Dexmedetomidine / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C494827:Bax protein, mouse; D016207:Cytokines; D016328:NF-kappa B; D020011:Protective Agents; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D020927:Dexmedetomidine; D003404:Creatinine; D002945:Cisplatin
keywords: Acute kidney injury; Apoptosis; Cisplatin; Dexmedetomidine; Inflammation