The effect of sildenafil on rats with adenine—Induced chronic kidney disease

Badreldin Ali, Mohammed A l Za'abi, Sirin Adham, Yousuf Al Suleimani, Turan Karaca, Priyadarsini Manoj, Jamila Al Kalbani, Javid Yasin, Abderrahim Nemmar

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Abstract

The erectile dysfunction drug sildenafil has cardiopulmonary protective actions, and a nephroprotective action in cisplatin and ischemia-reperfusion–induced acute kidney injury. Here, we assessed its possible ameliorative action in a model of chronic kidney disease (CKD) using adenine feeding. Eight groups of rats were treated with saline (controls), adenine (0.25% w/w in feed daily for 5 weeks), and oral sildenafil (0.1, 0.5 or 2.5 mg/kg), either alone, or concomitantly with adenine. Urine was collected 24 h after the end of the treatments from all rats and blood pressure measured, followed by collection of blood and kidneys for the measurement of several functional, biochemical and histopathological parameters. Adenine treatment reduced body weight, creatinine renal clearance, and increased water intake and urine output, as well as the plasma concentrations of urea and creatinine, neutrophil gelatinase-associated lipocalin, and N-acetyl-β-D-glucosaminidase activity, and albumin in urine. Adenine also increased the concentrations of the uremic toxins indoxyl sulfate, uric acid and phosphate, and a number of proteins and inflammatory cytokines, and decreased that of several anti – oxidant indices. Renal histopathological markers of damage (inflammation and fibrosis) were significantly increased by adenine. Sildenafil, given simultaneously with adenine, induced a dose - dependent improvements in most of the above parameters, suggesting its possible use as adjunct treatment for CKD in humans.

Original languageEnglish
Pages (from-to)391-402
Number of pages12
JournalBiomedicine and Pharmacotherapy
Volume108
DOIs
Publication statusPublished - Dec 1 2018

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Adenine
Chronic Renal Insufficiency
Urine
Kidney
Creatinine
Indican
Hexosaminidases
Erectile Dysfunction
Sildenafil Citrate
Uric Acid
Acute Kidney Injury
Oxidants
Cisplatin
Drinking
Urea
Albumins
Fibrosis
Ischemia
Phosphates
Body Weight

Keywords

  • Adenine
  • Chronic kidney disease
  • Nephroprotection
  • Rats
  • Sildenafil

ASJC Scopus subject areas

  • Pharmacology

Cite this

The effect of sildenafil on rats with adenine—Induced chronic kidney disease. / Ali, Badreldin; A l Za'abi, Mohammed; Adham, Sirin; Al Suleimani, Yousuf; Karaca, Turan; Manoj, Priyadarsini; Al Kalbani, Jamila; Yasin, Javid; Nemmar, Abderrahim.

In: Biomedicine and Pharmacotherapy, Vol. 108, 01.12.2018, p. 391-402.

Research output: Contribution to journalArticle

Ali, Badreldin ; A l Za'abi, Mohammed ; Adham, Sirin ; Al Suleimani, Yousuf ; Karaca, Turan ; Manoj, Priyadarsini ; Al Kalbani, Jamila ; Yasin, Javid ; Nemmar, Abderrahim. / The effect of sildenafil on rats with adenine—Induced chronic kidney disease. In: Biomedicine and Pharmacotherapy. 2018 ; Vol. 108. pp. 391-402.
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