title: Human ghrelin protects animals from renal ischemia-reperfusion injury through the vagus nerve.
abstract: BACKGROUND
  Acute kidney injury secondary to renal ischemia and reperfusion injury is widely prevalent. Ghrelin, which is a stomach-derived peptide, has been shown to be anti-inflammatory. The purpose of this study was to examine whether human ghrelin has any beneficial effects after renal ischemia and reperfusion injury, and if so, whether ghrelin's action in renal ischemia and reperfusion injury is mediated by the vagus nerve.
  
  
  METHODS
  Male adult rats were subjected to renal ischemia and reperfusion by bilateral renal pedicle clamping for 60 min, treated intravenously with human ghrelin (4 nmol/rat) or normal saline (vehicle) immediately after reperfusion. After 24 h, the animals were killed and samples were harvested. In separate groups, subdiaphragmatic vagotomy prior to renal ischemia and reperfusion was performed, treated with human ghrelin or vehicle, and at 24 h, blood and organs were harvested.
  
  
  RESULTS
  Renal ischemia and reperfusion injury caused significant increases in the serum levels of tissue injury markers compared with the sham operation. Human ghrelin treatment attenuated serum creatinine and blood urea nitrogen significantly by 55% and 53%, and liver enzymes (aminotransferase [AST] and alanine aminotransferase [ALT]) by 20% and 24%, respectively, compared with the vehicle-treated groups. Tissue water contents, plasma and kidney interleukin-6, and kidney myeloperoxidase activity were decreased. Bcl-2/Bax ratio was increased, and histology of the kidneys was improved. More importantly, prior vagotomy abolished ghrelin's protective effect in tissue injury markers and tissue water contents in renal ischemia and reperfusion injured animals.
  
  
  CONCLUSIONS
  Human ghrelin treatment in renal ischemia and reperfusion injured rats attenuated systemic and kidney-specific inflammatory responses. The protection of human ghrelin in renal ischemia and reperfusion injury was mediated by the vagus nerve. These data suggest that ghrelin can be developed as a novel treatment for patients with acute kidney injury induced by renal ischemia and reperfusion injury.
authors.affiliation: Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center, Manhasset, NY 11030, USA.
authors.forename: Derry
authors.initials: D
authors.lastname: Rajan
authors.forename: Rongqian
authors.initials: R
authors.lastname: Wu
authors.forename: Kavin G
authors.initials: KG
authors.lastname: Shah
authors.forename: Asha
authors.initials: A
authors.lastname: Jacob
authors.forename: Gene F
authors.initials: GF
authors.lastname: Coppa
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D054439:Ghrelin / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects*; D014867:Water / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D054439:Ghrelin; D015850:Interleukin-6; D051028:bcl-2-Associated X Protein; D014867:Water; D003404:Creatinine; D009195:Peroxidase