title: Sildenafil attenuates inflammation and oxidative stress in pelvic ganglia neurons after bilateral cavernosal nerve damage.
abstract: Erectile dysfunction is a common complication for patients undergoing surgeries for prostate, bladder, and colorectal cancers, due to damage of the nerves associated with the major pelvic ganglia (MPG). Functional re-innervation of target organs depends on the capacity of the neurons to survive and switch towards a regenerative phenotype. PDE5 inhibitors (PDE5i) have been successfully used in promoting the recovery of erectile function after cavernosal nerve damage (BCNR) by up-regulating the expression of neurotrophic factors in MPG. However, little is known about the effects of PDE5i on markers of neuronal damage and oxidative stress after BCNR. This study aimed to investigate the changes in gene and protein expression profiles of inflammatory, anti-inflammatory cytokines and oxidative stress related-pathways in MPG neurons after BCNR and subsequent treatment with sildenafil. Our results showed that BCNR in Fisher-344 rats promoted up-regulation of cytokines (interleukin- 1 (IL-1) β, IL-6, IL-10, transforming growth factor β 1 (TGFβ1), and oxidative stress factors (Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, Myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), TNF receptor superfamily member 5 (CD40) that were normalized by sildenafil treatment given in the drinking water. In summary, PDE5i can attenuate the production of damaging factors and can up-regulate the expression of beneficial factors in the MPG that may ameliorate neuropathic pain, promote neuroprotection, and favor nerve regeneration.
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA 90059, USA. lgarcia@ddchemco.com.
authors.forename: Leah A
authors.initials: LA
authors.lastname: Garcia
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA 90059, USA. suhlaing@cdrewu.edu.
authors.forename: Su M
authors.initials: SM
authors.lastname: Hlaing
authors.affiliation: Department of Health and Life Science, College of Science and Health, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA. RichardGutierrez@cdrewu.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gutierrez
authors.affiliation: Department of Health and Life Science, College of Science and Health, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA. MariaSanchez@cdrewu.edu.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Sanchez
authors.affiliation: Los Angeles Biomedical Research Institute, Harbor-University of California Los Angeles, Torrance, CA 90502, USA. ikovanecz@labiomed.org.
authors.forename: Istvan
authors.initials: I
authors.lastname: Kovanecz
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA 90059, USA. joartaza@ucla.edu.
authors.forename: Jorge N
authors.initials: JN
authors.lastname: Artaza
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA 90059, USA. monicaferrini@cdrewu.edu.
authors.forename: Monica G
authors.initials: MG
authors.lastname: Ferrini
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005724:Ganglia / Q000378:metabolism* / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009417:Nerve Tissue / Q000293:injuries; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology; D010413:Penis / Q000294:innervation; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000494:pharmacology*; D059467:Transcriptome; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D000068677:Sildenafil Citrate; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D019255:NADPH Oxidases