Phosphodiesterase type-5 inhibitor and oxidative stress

Int J Immunopathol Pharmacol. 2008 Oct-Dec;21(4):879-89. doi: 10.1177/039463200802100412.

Abstract

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Numerous physical and psychological factors are involved in normal erectile function, including neurological, vascular, hormonal and cavernous functions. The current therapy for the condition is pharmacological and psychotherapeutic which regulates the erectile function and amplifies the NO-mediated response. The aim of this work is to test the action of three common phosphodiesterase inhibitors: Tadalafil, Sildenafil Citrate and Vardenafil at 0.05 microM on human monocytes, analyzing the expression of iNOS protein and mRNA by Western blot and rt-PCR, and production of NO by conversion of L-(2,3,4,5)-[3H]Arginine to L-(3H) citrulline. We also tested the efficiency of the antioxidant network by spectrophotometer (SOD, CAT, GPx and Gr), under normal conditions and after stimulation with LPS. The results showed an increase in ROS levels, similar for all the molecules with regard to the antioxidant enzymes. In all cases the treatment determines a response to the limited efficiency, arriving at a situation in which phosphodiesterase inhibitors + LPS clearly show oxidative stress.

MeSH terms

  • Base Sequence
  • Blotting, Western
  • Catalase / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / drug effects*
  • DNA Primers
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Humans
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidative Stress*
  • Phosphodiesterase Inhibitors / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Superoxide Dismutase / metabolism
  • Superoxides / metabolism

Substances

  • DNA Primers
  • Phosphodiesterase Inhibitors
  • Superoxides
  • Catalase
  • Glutathione Peroxidase
  • Nitric Oxide Synthase Type II
  • Superoxide Dismutase
  • Glutathione Reductase
  • Cyclic Nucleotide Phosphodiesterases, Type 5