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.

MATERIALS AND 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.

CONCLUSION:

•  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: Monica G Ferrini, Joanne Moon, Steve Rivera, Jacob Rajfer, Nestor F Gonzalez-Cadavid
• Journal: BJU international (BJU Int) Vol. 109 Issue 4 Pg. 586-93 (Feb 2012) ISSN: 1464-410X [Electronic] England
• PMID: 21851542 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Chemical References

• Antioxidants
• Decorin
• Enzyme Inhibitors
• Nitric Oxide Donors
• Transforming Growth Factor beta1
• Allopurinol
• Molsidomine
• Nitric Oxide Synthase Type II

Topics

• Allopurinol (pharmacology)
• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Decorin (pharmacology)
• Diabetes Mellitus, Experimental (complications)
• Enzyme Inhibitors (pharmacology)
• Fibrosis (prevention & control)
• Male
• Mice
• Mice, Knockout
• Molsidomine (pharmacology)
• Muscle, Smooth (drug effects)
• Nitric Oxide Donors (pharmacology)
• Nitric Oxide Synthase Type II (deficiency)
• Oxidative Stress
• Penis (pathology)
• Transforming Growth Factor beta1 (antagonists & inhibitors)