ATP-sensitive potassium channel blockage attenuates cisplatin-induced renal damage.
BACKGROUND
Cisplatin-induced renal damage was associated with an inflammatory process. ATP-sensitive potassium channels can be involved in neutrophil migration. This study evaluated the effects of glibenclamide, an ATP-sensitive potassium channel blocker, on cisplatin-induced renal damage.


METHODS
A total of 48 Wistar rats received glibenclamide (20 mg/kg/day, s.c.) and 24 h later, these animals, and an additional group of 45 rats, were injected with cisplatin (5 mg/kg, i.p.). In addition, 38 control rats were injected with saline, i.p. Twenty-four hours and 5 days after saline or cisplatin injections blood and urine samples were collected to evaluate renal function and the kidneys were removed for analysis of neutrophil accumulation, tumor necrosis factor-alpha and interleukin-1beta and histological and immunohistochemical studies.


RESULTS
Cisplatin injection induced neutrophil recruitment and increased tumor necrosis factor-alpha and interleukin-1beta contents in renal cortices and outer medullae tissues. Cisplatin-treated rats also presented reduction in the glomerular filtration rate, as well as greater immunostaining for ED1 (macrophages/monocytes) and acute tubular necrosis. All of these alterations were reduced by treatment with glibenclamide. These effects seem to be related, at least in part, to the restriction of neutrophil recruitment and inflammatory process observed in the kidneys from glibenclamide+cisplatin-treated rats.
Flávio
Andréa G C
AG
Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Cunha
Fernando Q
FQ
Francescato
Heloísa D Colletta
HD
Soares
Telma J
TJ
Costa
Roberto S
RS
Barbosa Júnior
Fernando
F
Coimbra
Terezila M
TM
D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D002945:Cisplatin