Publication: 5-aminoisoquinoline improves renal function and fibrosis during recovery phase of cisplatin-induced acute kidney injury in rats.
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Date
2018-04-27
Authors
Quesada, Andrés
O'Valle, Francisco
Montoro-Molina, Sebastián
Gómez-Morales, Mercedes
Caba-Molina, Mercedes
González, Juan Francisco
de Gracia, María C
Osuna, Antonio
Vargas, Félix
Wangensteen, Rosemary
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Abstract
The aim of the present 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 (CisPt)-induced acute kidney injury (AKI) in rats. Male Wistar rats were distributed in three groups (n=8 each group): control, CisPt, and CisPt + 5-AIQ. Control and CisPt groups received a subcutaneous injection of either saline or 7 mg/kg CisPt, respectively. CisPt + 5-AIQ group received two intraperitoneal injections of 10 mg/kg 5-AIQ 2 h before and 24 h after CisPt treatment. Thirteen days after the treatment, rats were housed in metabolic cages and 24-h urine collection was made. At day 14, CisPt-treated rats showed increased diuresis, N-acetyl-β-d-glucosaminidase (NAG) excretion, glucosuria and sodium fractional excretion (NaFE), and decreased creatinine clearance (CrCl). 5-AIQ significantly increased CrCl and decreased NAG excretion, glucosuria, and NaFE. In plasma, CisPt increased sodium, urea, and creatinine concentrations, while 5-AIQ treatment decreased these variables to the levels of control group. 5-AIQ completely prevented the body weight loss evoked by CisPt treatment. CisPt 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 the CisPt treatment, preventing renal dysfunction and body weight decrease and ameliorating tubular lesions and collagen deposition.
Description
MeSH Terms
Acute Kidney Injury
Animals
Cisplatin
Fibrosis
Isoquinolines
Kidney
Kidney Function Tests
Male
Rats
Rats, Wistar
Animals
Cisplatin
Fibrosis
Isoquinolines
Kidney
Kidney Function Tests
Male
Rats
Rats, Wistar
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CIE Terms
Keywords
5-aminoisoquinoline, cisplatin, kidney, renal dysfunction, renal fibrosis