title: Exendin-4 and sitagliptin protect kidney from ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction.
abstract: BACKGROUND
  This study tested the hypothesis that exendin-4 and sitagliptin can effectively protect kidney from acute ischemia-reperfusion (IR) injury.
  
  
  METHODS
  Adult SD-rats (n = 48) equally divided into group 1 (sham control), group 2 (IR injury), group 3 [IR + sitagliptin 600 mg/kg at post-IR 1, 24, 48 hr)], and group 4 [IR + exendin-4 10 μm/kg at 1 hr after procedure] were sacrificed after 24 and 72 hrs (n = 6 at each time from each group) following clamping of bilateral renal pedicles for 60 minutes (groups 2-4).
  
  
  RESULTS
  Serum creatinine level and urine protein to creatinine ratio were highest in group 2 and lowest in group 1 (all p < 0.001) without notable differences between groups 3 and 4. Kidney injury score, expressions of inflammatory biomarkers at mRNA (MMP-9, TNF-α, IL-1β, PAI-1), protein (TNF-α, NF-κB and VCAM-1), and cellular (CD68+) levels in injured kidneys at 24 and 72 hr showed an identical pattern compared to that of creatinine level in all groups (all p < 0.0001). Expressions of oxidized protein, reactive oxygen species (NOX-1, NOX-2), apoptosis (Bax, caspase-3 and PARP), and DNA damage marker (γH2AX+) of IR kidney at 24 and 72 hrs exhibited a pattern similar to that of inflammatory mediators among all groups (all p < 0.01). Renal expression of glucagon-like peptide-1 receptor, and anti-oxidant biomarkers at cellular (GPx, GR) and protein (NQO-1, HO-1, GPx) levels at 24 and 72 hr were lowest in group 1, significantly lower in group 2 than in groups 3 and 4 (all p < 0.01).
  
  
  CONCLUSIONS
  Exendin-4 and sitagliptin provided significant protection for the kidneys against acute IR injury.
authors.forename: Yen-Ta
authors.initials: YT
authors.lastname: Chen
authors.forename: Tzu-Hsien
authors.initials: TH
authors.lastname: Tsai
authors.forename: Chih-Chau
authors.initials: CC
authors.lastname: Yang
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Li-Teh
authors.initials: LT
authors.lastname: Chang
authors.forename: Hung-Hwa
authors.initials: HH
authors.lastname: Chen
authors.forename: Chia-Lo
authors.initials: CL
authors.lastname: Chang
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Sung
authors.forename: Yen-Yi
authors.initials: YY
authors.lastname: Zhen
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Hsueh-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Dapi Road, Niaosung Dist,, Kaohsiung city 83301, Taiwan. han.gung@msa.hinet.net.
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D000077270:Exenatide; D007249:Inflammation / Q000517:prevention & control*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D011507:Proteinuria / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000517:prevention & control*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D010455:Peptides; D011719:Pyrazines; D014230:Triazoles; D014688:Venoms; D000077270:Exenatide; D003404:Creatinine; D000068900:Sitagliptin Phosphate