PMID- 25264738 OWN - NLM STAT- MEDLINE DCOM- 20150603 LR - 20211021 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 15 IP - 10 DP - 2014 Sep 26 TI - Sildenafil attenuates inflammation and oxidative stress in pelvic ganglia neurons after bilateral cavernosal nerve damage. PG - 17204-20 LID - 10.3390/ijms151017204 [doi] AB - 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) beta, IL-6, IL-10, transforming growth factor beta 1 (TGFbeta1), 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. FAU - Garcia, Leah A AU - Garcia LA AD - 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. FAU - Hlaing, Su M AU - Hlaing SM AD - 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. FAU - Gutierrez, Richard A AU - Gutierrez RA AD - 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. FAU - Sanchez, Maria D AU - Sanchez MD AD - 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. FAU - Kovanecz, Istvan AU - Kovanecz I AD - Los Angeles Biomedical Research Institute, Harbor-University of California Los Angeles, Torrance, CA 90502, USA. ikovanecz@labiomed.org. FAU - Artaza, Jorge N AU - Artaza JN AD - 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. FAU - Ferrini, Monica G AU - Ferrini MG AD - 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. LA - eng GR - U54 MD007598/MD/NIMHD NIH HHS/United States GR - 5U54MD007598-05/MD/NIMHD NIH HHS/United States GR - 5S21 MD000103/MD/NIMHD NIH HHS/United States GR - SC1NS064611/NS/NINDS NIH HHS/United States GR - SC1 NS064611/NS/NINDS NIH HHS/United States GR - U54MD008149/MD/NIMHD NIH HHS/United States GR - S21 MD000103/MD/NIMHD NIH HHS/United States GR - U54 MD008149/MD/NIMHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140926 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Cytokines) RN - 0 (Phosphodiesterase 5 Inhibitors) RN - 0 (Piperazines) RN - 0 (Purines) RN - 0 (Sulfonamides) RN - BW9B0ZE037 (Sildenafil Citrate) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.6.3.- (NADPH Oxidases) SB - IM MH - Animals MH - Cytokines/genetics/metabolism MH - Disease Models, Animal MH - Ganglia/*metabolism/pathology MH - Heme Oxygenase-1/genetics/metabolism MH - Male MH - NADPH Oxidases/genetics/metabolism MH - Nerve Tissue/injuries MH - Nitric Oxide Synthase Type II/metabolism MH - Oxidative Stress/*drug effects MH - Penile Erection/drug effects/physiology MH - Penis/innervation MH - Phosphodiesterase 5 Inhibitors/*pharmacology MH - Piperazines/*pharmacology MH - Purines/pharmacology MH - Rats MH - Rats, Inbred F344 MH - Sildenafil Citrate MH - Sulfonamides/*pharmacology MH - Transcriptome MH - Up-Regulation/drug effects PMC - PMC4227157 EDAT- 2014/09/30 06:00 MHDA- 2015/06/04 06:00 PMCR- 2014/10/01 CRDT- 2014/09/30 06:00 PHST- 2014/07/13 00:00 [received] PHST- 2014/09/09 00:00 [revised] PHST- 2014/09/16 00:00 [accepted] PHST- 2014/09/30 06:00 [entrez] PHST- 2014/09/30 06:00 [pubmed] PHST- 2015/06/04 06:00 [medline] PHST- 2014/10/01 00:00 [pmc-release] AID - ijms151017204 [pii] AID - ijms-15-17204 [pii] AID - 10.3390/ijms151017204 [doi] PST - epublish SO - Int J Mol Sci. 2014 Sep 26;15(10):17204-20. doi: 10.3390/ijms151017204.