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

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.