Objectives: 

It has been reported that poly (ADP-ribose) polymerase-1 (PARP1) needs to be activated for cisplatin nephrotoxicy. The aim of this work is to study the effects of 5-aminoisoquinoline (5-AIQ), a PARP1 inhibitor, over renal dysfunction in cisplatin-treated rats.

Materials: 

24 male Wistar rats weighing 227-280g were distributed in three groups: Control, CisPt and CisPt+AIQ. Control and CisPt groups received a subcutaneous injection of either saline or 7 mg/kg cisplatin, respectively. CisPt+AIQ group received two i.p. injection of 10 mg/kg of 5-AIQ 24 and 2 hours before cisplatin treatment. 14 days after treatment, rats were housed in metabolic cages and 24-h urine collection was made. At the end of the experiment, blood samples were obtained from left ventricle under anesthesia (pentobarbital, 50 mg/Kg, i.p) and kidneys were dissected and weighted. We used t test for statistical comparisons, and Welch modification of t test when variances were different.

Results: 

Cisplatin-treated rats showed an increased diuresis, glucosuria, NAG and sodium excretional fractium (NaEF), and a decreased urine creatinine content, creatinine clearance (CrCl), sodium tubular load (NaTL) and sodium reabsortion (NaR). 5-AIQ completely prevented the increases in glucosuria, NAG and NaEF, and also restored urine creatinine content, CrCl, NaTL and NaR at the levels of control group. In plasma, CisPt group showed increases in sodium, urea and creatinine concentration, while these parameters remained unchanged in CisPt+AIQ group versus control group. 5-AIQ also improved the ratio kidney weight/body weight and the body weight increase of CisPt group, from -13.98 ± 1.86 to 20.11 ± 1.45 in CisPt+AIQ group, that was similar to Control group (20.5 ± 4.42 % of their corresponding initial body weight).

Conclusions: 

5-AIQ administration produced a remarkable improvement in long-term renal function of cisplatin-treated rats, and also ameliorated morphological parameters as kidney weight/body weight ratio and body weight increase.