5-aminoisoquinoline improves renal function and fibrosis during recovery phase of cisplatin-induced acute kidney injury in rats

Autor: Quesada, Andrés, O'Valle Ravassa, Francisco Javier, Montoro-Molina, Sebastián, Gómez-Morales, Mercedes, Caba Molina, Mercedes, González, Juan Francisco, de Gracia, María C., Osuna Ortega, Antonio|||0000-0001-5938-7375, Vargas, Félix, Wangensteen, Rosemary
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Digibug. Repositorio Institucional de la Universidad de Granada
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Popis: 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.
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’.
Databáze: OpenAIRE
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