title: Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant function.
abstract: Renal injury induced by brain death is characterized by ischemia and inflammation, and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 h of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 h of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain-dead rats showed significant improvement in function over the first 2 to 4 days after transplantation compared with untreated brain-dead animals. Gene microarray analysis after 2 h of brain death without or with nitrite therapy showed that the latter significantly altered the expression of about 400 genes. Ingenuity Pathway Analysis indicated that multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription, and genes related to humoral immune responses. Thus, nitrite therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function.
authors.affiliation: Department of Biochemistry, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Kelpke
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Kelley M
authors.initials: KM
authors.lastname: Bradley
authors.forename: Xinjun
authors.initials: X
authors.lastname: Teng
authors.forename: Phillip
authors.initials: P
authors.lastname: Chumley
authors.forename: Angela
authors.initials: A
authors.lastname: Brandon
authors.forename: Brett
authors.initials: B
authors.lastname: Yancey
authors.forename: Brandon
authors.initials: B
authors.lastname: Moore
authors.forename: Hughston
authors.initials: H
authors.lastname: Head
authors.forename: Liliana
authors.initials: L
authors.lastname: Viera
authors.forename: John A
authors.initials: JA
authors.lastname: Thompson
authors.forename: David K
authors.initials: DK
authors.lastname: Crossman
authors.forename: Molly S
authors.initials: MS
authors.lastname: Bray
authors.forename: Devin E
authors.initials: DE
authors.lastname: Eckhoff
authors.forename: Anupam
authors.initials: A
authors.lastname: Agarwal
authors.forename: Rakesh P
authors.initials: RP
authors.lastname: Patel
mesh_terms: D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001926:Brain Death / Q000503:physiopathology*; D015870:Gene Expression / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000517:prevention & control; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology; D016030:Kidney Transplantation / Q000379:methods* / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009573:Nitrites / Q000097:blood; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D012977:Sodium Nitrite / Q000008:administration & dosage*
chemical_list: D001565:Benzoates; D007093:Imidazoles; D009573:Nitrites; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D000493:Allopurinol; D012977:Sodium Nitrite