The ATP-sensitive potassium channel blocker glibenclamide prevents renal ischemia/reperfusion injury in rats.
BACKGROUND
Renal ischemia/reperfusion (I/R) is a complex neutrophil-mediated syndrome. Adenosine-triphosphate (ATP)-sensitive potassium (K(ATP)) channels are involved in neutrophil migration in vivo. In the present study, we have investigated the effects of glibenclamide, a K(ATP) channel blocker, in renal I/R injury in rats.


METHODS
The left kidney of the rats was excised through a flank incision and ischemia was performed in the contralateral kidney by total interruption of renal artery flow for 45 minutes. Renal perfusion was reestablished, and the kidney and lungs were removed for analysis of vascular permeability, neutrophil accumulation, and content of cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-10] 4 and 24 hours later. Renal function was assessed by measuring creatinine, Na(+), and K(+) levels in the plasma and by determination of creatinine clearance. Drugs were administered subcutaneously after the onset of ischemia.


RESULTS
Reperfusion of the ischemic kidney induced local (kidney) and remote (lung) inflammatory injury and marked renal dysfunction. Glibenclamide (20 mg/kg) significantly inhibited the reperfusion-associated increase in vascular permeability, neutrophil accumulation, increase in TNF-alpha levels and nuclear factor-kappaB (NF-kappaB) translocation. These inhibitory effects were noticed in the kidney and lungs. Moreover, glibenclamide markedly ameliorated the renal dysfunction at 4 and 24 hours.


CONCLUSIONS
Treatment with glibenclamide is associated with inhibition of neutrophil recruitment and amelioration of renal dysfunction following renal I/R. Glibenclamide may have a therapeutic role in the treatment of renal I/R injury, such as after renal transplantation.
Pompermayer
Kenia
K
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas-Universidade Federal de Minas Gerais, Brazil.
Souza
Danielle G
DG
Lara
Giovanna G
GG
Silveira
Kátia D
KD
Cassali
Geovanni D
GD
Andrade
Anderson A
AA
Bonjardim
Cláudio A
CA
Passaglio
Kátia T
KT
Assreuy
Jamil
J
Cunha
Fernando Q
FQ
Vieira
Maria Aparecida R
MA
Teixeira
Mauro M
MM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology; D004195:Disease Models, Animal; D005905:Glyburide / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D016328:NF-kappa B; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014409:Tumor Necrosis Factor-alpha; C117780:mitochondrial K(ATP) channel; D016753:Interleukin-10; D000255:Adenosine Triphosphate; D003981:Diazoxide; D005905:Glyburide