title: Influence of sildenafil and donepezil administration on the serum redox balance in experimentally induced lower limb critical ischemia.
abstract: BACKGROUND
  Chronic lower limb ischemia (CLLI) leads to endothelial cell dysfunctions and endothelial lesions. The use of substances that release nitric oxide and activate endothelial nitric oxide synthase has proved to be useful in increasing angiogenesis and arteriogenesis under critical ischemia conditions.
  
  
  OBJECTIVE
  To investigate the therapeutic effect of Sildenafil and Donepezil with a vasodilating action in experimentally induced CLLI and on serum redox homeostasis.
  
  
  METHODS
  The research was performed in 3 groups of rats (n=10 animals/group) with experimentally induced CLLI: group I - control group; group II - animals treated postoperatively with a therapeutic dose of sildenafil, and group III - animals treated postoperatively with a therapeutic dose of donepezil. Oxidative stress (OS) indicators (malondialdehyde - MDA, protein carbonyls - PC), antioxidant (AO) defense indicators (reduced glutathione - GSH and oxidized glutathione - GSSH), and ceruloplasmin (CP) were determined on days 7, 14, 21 and 30. Statistical processing was performed using the Excel application (Microsoft Office 2007), with the StatsDirect v.2.7.2 software.
  
  
  RESULTS
  Changes in OS were evidenced in all groups on account of a decrease in MDA and PC. The greatest OS decrease in all groups was on day 30. AO defence changes were represented by decreased levels of GSH and GSSG in all groups, at the studied moments. Intracellular AO defense in the cytosol, nucleus and mitochondria was similar in all groups, (decreased GSH, GSSG and GSH/GSSG ratio). We found increased extracellular levels of GSH, GSSG, and CP and increased extracellular GSH/GSSG ratio at level compared to values on day 7.
  
  
  CONCLUSIONS
  1) The administration of sildenafil (group II) and donepezil (group III) has favorable effects on reducing OS in experimentally induced CLLI. 2) Sildenafil and Donepezil administration stimulates extracellular AO defense on account of CP. 3) Sildenafil and Donepezil administration influences intracellular redox homeostasis on account of the GSH/GSSG couple, the major redox buffer in the body.
authors.affiliation: 2 Surgical Clinic, County Clinic Hospital, Cluj-Napoca, Romania.
authors.forename: Mihaela Ioana
authors.initials: MI
authors.lastname: Constantinescu
authors.affiliation: 4 Surgical Clinic, County Clinic Hospital, Cluj-Napoca, Romania.
authors.forename: Dan Petru
authors.initials: DP
authors.lastname: Constantinescu
authors.affiliation: 2 Surgical Clinic, County Clinic Hospital, Cluj-Napoca, Romania.
authors.forename: Aurel
authors.initials: A
authors.lastname: Andercou
authors.affiliation: 2 Surgical Clinic, County Clinic Hospital, Cluj-Napoca, Romania.
authors.forename: Ion Aurel
authors.initials: IA
authors.lastname: Mironiuc
keywords: Donepezil; Sildenafil; antioxidant defence; chronic ischemia; lower limb; oxidative stress