@misc{10481/54731,
year = {2018},
month = {4},
url = {http://hdl.handle.net/10481/54731},
abstract = {The aim of this study is to analyze the effects of 5-aminoisoquinoline (5-AIQ), a
poly(ADP-ribose) polymerase-1 (PARP1) inhibitor, over renal dysfunction and fibrosis
during recovery phase of cisplatin-induced acute kidney injury (AKI) in rats. Male
Wistar rats were distributed in three groups (n=8 each group): control, cisplatin (CisPt)
and CisPt+5-AIQ. Control and CisPt groups received a subcutaneous injection of either
saline or 7 mg/kg cisplatin, respectively. CisPt+5-AIQ group received two
intraperitoneal injections of 10 mg/kg 5-AIQ 2 hours before and 24 hours after cisplatin
treatment. 13 days after treatment, rats were housed in metabolic cages and 24-h urine
collection was made. At day 14, cisplatin-treated rats showed increased diuresis, Nacetyl-
β-D-glucosaminidase (NAG) excretion, glucosuria and sodium fractional
excretion, and decreased creatinine clearance (CrCl). 5-AIQ significantly increased
CrCl and decreased NAG excretion, glucosuria and sodium fractional excretion. In
plasma, cisplatin increased sodium, urea and creatinine concentration, while 5-AIQ
treatment decreased these variables to the levels of control group. 5-AIQ completely
prevented the body weight loss evoked by cisplatin treatment. Cisplatin also induced an
increased renal expression of PAR polymer, α-smooth muscle actin (α-SMA),
transforming growth factor-β1 (TGF-β1) and collagen-IV. These variables were
decreased in CisPt+5-AIQ group. Tubular lesions and renal fibrosis were also decreased
by 5-AIQ treatment. We conclude that inhibition of PARP1 with 5-AIQ can attenuate
long-term nephrotoxic effects associated with cisplatin treatment, preventing renal
dysfunction and body weight decrease, and ameliorating tubular lesions and collagen
deposition.},
organization = {This work was supported by the Carlos III Health Institute of Spain [grant numbers PI13/02743, PI13/02384]; the Red de Investigación Renal REDinREN [grant number RD16/0009/0033]; ‘FEDER una manera de hacer Europa’.},
keywords = {5-aminoisoquinoline},
keywords = {Cisplatin},
keywords = {Renal fibrosis},
title = {5-aminoisoquinoline improves renal function and fibrosis during recovery phase of cisplatin-induced acute kidney injury in rats},
author = {Quesada, Andrés and O'Valle Ravassa, Francisco Javier and Montoro-Molina, Sebastián and Gómez-Morales, Mercedes and Caba Molina, Mercedes and González, Juan Francisco and de Gracia, María C. and Osuna Ortega, Antonio and Vargas, Félix and Wangensteen, Rosemary},
}