5-aminoisoquinoline improves renal function and fibrosis during recovery phase of cisplatin-induced acute kidney injury in rats 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 Vargas, Félix Wangensteen, Rosemary 5-aminoisoquinoline Cisplatin Renal fibrosis 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. 2019-02-13T12:46:50Z 2019-02-13T12:46:50Z 2018-04 info:eu-repo/semantics/article Quesada, Andrés; O'Valle, Francisco; Montoro-Molina, Sebastián; Gómez-Morales, Mercedes; Caba Molina, Mercedes; González, Juan Francisco; de Gracia, María C.; Osuna Ortega, Antonio; Vargas, Félix; Wangensteen, Rosemary. 5-aminoisoquinoline improves renal function and fibrosis during recovery phase of cisplatin-induced acute kidney injury in rats. Bioscience Reports. vol. 38 no. 2. [http://hdl.handle.net/10481/54731] 0144-8463 1573-4935 http://hdl.handle.net/10481/54731 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España