Poly(adenosine diphosphate-ribose) polymerase inhibition preserves erectile function in rats after cavernous nerve injury

Muammer Kendirci, Zsuzsanna Zsengellér, Trinity J. Bivalacqua, Serap Gur, Mustafa F. Usta, Min Chen, Csaba Szabo, Wayne J G Hellstrom

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Purpose: We investigated the involvement of poly(adenosine diphosphate-ribose) (PAR) polymerase (PARP) activation in the development of erectile dysfunction and the therapeutic benefit of the potent PARP inhibitor INO-1001 (Inotek Pharmaceuticals Corp., Beverly, Massachusetts) in a bilateral cavernous nerve crush injury (BCNCI) model in rats. Materials and Methods: Sprague-Dawley rats were divided into 3 groups, namely sham treated, BCNCI plus vehicle and BCNCI plus the PARP inhibitor INO-1001. One week after surgical intervention all groups underwent in vivo cavernous nerve stimulation. PAR activation, nitrotyrosine and inducible nitric oxide synthase were evaluated by immunohistochemistry and serum levels of INO-1001 were measured by high performance liquid chromatography. Penile tissues were analyzed for levels of malondialdehyde and myeloperoxidase. Data sets were statistically compared in all groups. Results: Neurogenic mediated erectile responses were evaluated. Mean intracavernous pressure (ICP), the ICP-to-blood-pressure ratio and total ICP were significantly decreased in BCNCI plus vehicle rats. These values were not statistically different between the sham and PARP inhibitor treated groups. There was a marked decrease in PAR staining in the treatment group. There was a substantial increase in malondialdehyde tissue levels but not myeloperoxidase in response to BCNCI, which was unchanged with PARP inhibitor treatment. There was a marked increase in tyrosine nitration in the treatment group. Up-regulation of nitric oxide synthase and increased tyrosine nitration were not observed in the penile tissues of the treatment group. Conclusions: These data demonstrate that BCNCI in a rat model causes increased PARP activation, resulting in severe erectile dysfunction. Treatment with the PARP inhibitor INO-1001 decreases the degree of nitrosative stress, prevents PARP activation and provides significant cavernous neuroprotection, which in turn preserves erectile function.

Original languageEnglish (US)
Pages (from-to)2054-2059
Number of pages6
JournalJournal of Urology
Volume174
Issue number5
DOIs
StatePublished - Nov 2005
Externally publishedYes

Fingerprint

Nerve Crush
Poly Adenosine Diphosphate Ribose
Wounds and Injuries
Adenosine Diphosphate Ribose
Erectile Dysfunction
Malondialdehyde
Pressure
Peroxidase
Tyrosine
Therapeutics
Nitric Oxide Synthase Type II
Nitric Oxide Synthase
Sprague Dawley Rats
Inhibition (Psychology)
Crush Injuries
Up-Regulation
Immunohistochemistry
High Pressure Liquid Chromatography
Staining and Labeling
Blood Pressure

Keywords

  • Nerves
  • Penis
  • Poly(ADP-ribose) polymerases
  • Prostatectomy
  • Rats, Sprague-Dawley

ASJC Scopus subject areas

  • Urology

Cite this

Kendirci, M., Zsengellér, Z., Bivalacqua, T. J., Gur, S., Usta, M. F., Chen, M., ... Hellstrom, W. J. G. (2005). Poly(adenosine diphosphate-ribose) polymerase inhibition preserves erectile function in rats after cavernous nerve injury. Journal of Urology, 174(5), 2054-2059. https://doi.org/10.1097/01.ju.0000176484.35636.e5

Poly(adenosine diphosphate-ribose) polymerase inhibition preserves erectile function in rats after cavernous nerve injury. / Kendirci, Muammer; Zsengellér, Zsuzsanna; Bivalacqua, Trinity J.; Gur, Serap; Usta, Mustafa F.; Chen, Min; Szabo, Csaba; Hellstrom, Wayne J G.

In: Journal of Urology, Vol. 174, No. 5, 11.2005, p. 2054-2059.

Research output: Contribution to journalArticle

Kendirci, M, Zsengellér, Z, Bivalacqua, TJ, Gur, S, Usta, MF, Chen, M, Szabo, C & Hellstrom, WJG 2005, 'Poly(adenosine diphosphate-ribose) polymerase inhibition preserves erectile function in rats after cavernous nerve injury', Journal of Urology, vol. 174, no. 5, pp. 2054-2059. https://doi.org/10.1097/01.ju.0000176484.35636.e5
Kendirci, Muammer ; Zsengellér, Zsuzsanna ; Bivalacqua, Trinity J. ; Gur, Serap ; Usta, Mustafa F. ; Chen, Min ; Szabo, Csaba ; Hellstrom, Wayne J G. / Poly(adenosine diphosphate-ribose) polymerase inhibition preserves erectile function in rats after cavernous nerve injury. In: Journal of Urology. 2005 ; Vol. 174, No. 5. pp. 2054-2059.
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AU - Kendirci, Muammer

AU - Zsengellér, Zsuzsanna

AU - Bivalacqua, Trinity J.

AU - Gur, Serap

AU - Usta, Mustafa F.

AU - Chen, Min

AU - Szabo, Csaba

AU - Hellstrom, Wayne J G

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