Sildenafil and tadalafil reduce the risk of contrast-induced nephropathy by modulating the oxidant/antioxidant balance in a murine model

Food Chem Toxicol. 2020 Jan:135:111038. doi: 10.1016/j.fct.2019.111038. Epub 2019 Dec 9.

Abstract

The aim of the study was to evaluate the potential protective role of sildenafil and tadalafil in contrast-induced nephropathy (CIN) by modulating oxidative stress. Thirty Wistar male rats were equally assigned into five groups: sham, CIN, CIN + sildenafil (10 mg/kg bw/day), CIN + tadalafil (5 mg/kg bw/day) and CIN + N-Acetyl Cysteine (NAC) (100 mg/kg bw/day) as a positive control. CIN was induced by 12 h dehydration and administration of indomethacin (10 mg/kg bw), N-ω- nitro-L-arginine methyl ester (10 mg/kg bw), and iopromide (3 g/kg bw iodine). Blood was drawn prior to and 24 h after CIN induction for evaluating renal function and oxidative stress. In the CIN group, total antioxidant capacity (TAC), reduced glutathione (GSH) and catalase (CAT) levels were significantly decreased; and protein carbonyl (PROTC) and thiobarbituric reactive species (TBARS) were significantly increased compared to the sham group. Pre- Sildenafil and tadalafil pre-treatment reduced CIN risk and reversed oxidative stress almost to the sham group levels. These results suggest that PDE5Is can be good candidates for preventing CIN based on their ability to modulate the oxidant/antioxidant balance.

MeSH terms

  • Acetylcysteine / administration & dosage
  • Animals
  • Antioxidants / metabolism*
  • Catalase / metabolism
  • Contrast Media / adverse effects*
  • Disease Models, Animal
  • Glutathione / metabolism
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / enzymology
  • Kidney Diseases / metabolism
  • Kidney Diseases / prevention & control*
  • Male
  • Mice
  • Oxidants / metabolism*
  • Oxidative Stress
  • Phosphodiesterase 5 Inhibitors / pharmacology*
  • Rats
  • Rats, Wistar
  • Sildenafil Citrate / pharmacology*
  • Tadalafil / pharmacology*
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Antioxidants
  • Contrast Media
  • Oxidants
  • Phosphodiesterase 5 Inhibitors
  • Thiobarbituric Acid Reactive Substances
  • Tadalafil
  • Sildenafil Citrate
  • Catalase
  • Glutathione
  • Acetylcysteine