Effects of Sildenafil Citrate on Hepatic Function and Regeneration in Normal and Alcohol-Fed Rats

Liver Int. 2005 Aug;25(4):913-9. doi: 10.1111/j.1478-3231.2005.01061.x.

Abstract

Sildenafil citrate is a potent inhibitor of specific phosphodiesterase-5, which mediates metabolism of intracellular second message -- cGMP. Sildenafil citrate has been widely used for erectile dysfunction in men. Moreover, it is known that men with liver diseases have higher rate of erectile dysfunction. Furthermore, it has been demonstrated that nitric oxide plays an important role in liver function and regeneration. The present study evaluates effects of sildenafil citrate on hepatic function and regeneration in normal and alcohol-fed rats. In normal rats sildenafil citrate has a trend to improve hepatic function after partial hepatectomy (PHx). Moreover, sildenafil citrate significantly reduces hepatic regenerative activity at the concentration of 5 mg/kg body weight. However, sildenafil had no effects on hepatic function and regeneration of alcohol-fed rats. In general, sildenafil citrate did not induce significant changes in hepatic function and regenerative activity after PHx in normal and alcohol-fed rats, except at concentration of 5 mg/kg sildenafil citrate significantly inhibit hepatic regeneration in normal rats.

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Animals
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Dose-Response Relationship, Drug
  • Ethanol / toxicity*
  • Gene Expression / drug effects
  • Hepatectomy
  • Liver / drug effects*
  • Liver / physiology
  • Liver / surgery
  • Liver Diseases, Alcoholic / metabolism
  • Liver Diseases, Alcoholic / pathology*
  • Liver Regeneration / drug effects*
  • Liver Regeneration / physiology
  • Male
  • Phosphodiesterase Inhibitors / toxicity*
  • Phosphoric Diester Hydrolases / genetics
  • Phosphoric Diester Hydrolases / metabolism
  • Piperazines / toxicity*
  • Purines
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sildenafil Citrate
  • Sulfones

Substances

  • Phosphodiesterase Inhibitors
  • Piperazines
  • Purines
  • RNA, Messenger
  • Sulfones
  • Ethanol
  • Sildenafil Citrate
  • Phosphoric Diester Hydrolases
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Pde5a protein, rat