title: Amelioration of diabetes-induced cavernosal fibrosis by antioxidant and anti-transforming growth factor-β1 therapies in inducible nitric oxide synthase-deficient mice.
abstract: OBJECTIVE
  •  To investigate whether sustained long-term separate treatments of diabetic inducible nitric oxide synthase knockout (iNOSKo) mice with allopurinol, an antioxidant inhibiting xanthine oxidoreductase, decorin, a transforming growth factor-β1 (TGFβ1) -binding antagonist, and molsidomine, a long-life nitric oxide donor, prevent the processes of diabetes-induced cavernosal fibrosis.
  
  
  METHODS
  •  Eight week old male iNOS knock out (iNOSKo) mice were made diabetic by injecting 150 mg/kg B.W Streptozotocin (1P) with were either left untreated or treated with the oral antioxidant allopurinol (40 mg/kg/day), or decoin (50 mg, 1P, twice), as an anti-TGFβ1 agent (n = 8/group). •  Glycemia and oxidative stress markers were determined in blood and urine. •  Paraffin-embedded tissue sections from the penile shaft were subjected to Masson trichrome staining for the smooth muscle (smc)/collagen ratio, and imunostaining for smc content, profibrotic factors, oxidative stress, cell replication and cell death markers followed by quantitative image analysis.
  
  
  RESULTS
  •  Eight-week treatment with either allopurinol or decorin counteracted the decrease in smooth muscle cells and the increase in apoptosis and local oxidative stress within the corpora tissue. •  Decorin but not allopurinol increased the smooth muscle cell/collagen ratio, whereas allopurinol but not decorin inhibited systemic oxidative stress. •  Molsidomine was effective in reducing both local and systemic oxidative stress, but did not prevent corporal fibrosis.
  
  
  CONCLUSIONS
  •  Both allopurinol and decorin appear as promising approaches either as a single or a combined pharmacological modality for protecting the diabetic corpora from undergoing apoptosis and fibrosis although their functional effects still need to be defined.
authors.affiliation: Department of Internal Medicine, Charles R. Drew University Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. monicaferrini@cdrewu.edu
authors.forename: Monica G
authors.initials: MG
authors.lastname: Ferrini
authors.forename: Joanne
authors.initials: J
authors.lastname: Moon
authors.forename: Steve
authors.initials: S
authors.lastname: Rivera
authors.forename: Jacob
authors.initials: J
authors.lastname: Rajfer
authors.forename: Nestor F
authors.initials: NF
authors.lastname: Gonzalez-Cadavid
mesh_terms: D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D058575:Decorin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005355:Fibrosis / Q000517:prevention & control; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008981:Molsidomine / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency*; D018384:Oxidative Stress; D010413:Penis / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors*
chemical_list: D000975:Antioxidants; D058575:Decorin; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D053773:Transforming Growth Factor beta1; D000493:Allopurinol; D008981:Molsidomine; D052247:Nitric Oxide Synthase Type II