Sildenafil Attenuates Inflammation and Oxidative Stress in Pelvic Ganglia Neurons after Bilateral Cavernosal Nerve Damage

Autor: Richard A. Gutierrez, Leah A. Garcia, Monica G. Ferrini, María Díaz Sánchez, Su M Hlaing, Istvan Kovanecz, Jorge N. Artaza
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
sildenafil
Nitric Oxide Synthase Type II
medicine.disease_cause
Piperazines
lcsh:Chemistry
chemistry.chemical_compound
Neurotrophic factors
Nerve Tissue
lcsh:QH301-705.5
Spectroscopy
Sulfonamides
NADPH oxidase
biology
Heme oxygenase 1
Penile Erection
General Medicine
Up-Regulation
3. Good health
Computer Science Applications
Nitric oxide synthase
Myeloperoxidase
medicine.symptom
Nicotinamide adenine dinucleotide phosphate
medicine.medical_specialty
Inflammation
Neuroprotection
Article
Sildenafil Citrate
Catalysis
Inorganic Chemistry
Internal medicine
medicine
Animals
Physical and Theoretical Chemistry
Molecular Biology
Organic Chemistry
inducible nitric oxide synthase
NADPH Oxidases
Phosphodiesterase 5 Inhibitors
bilateral cavernosal nerve damage
Rats
Inbred F344
cytokines
Rats
Disease Models
Animal
Oxidative Stress
Endocrinology
chemistry
lcsh:Biology (General)
lcsh:QD1-999
Purines
biology.protein
Ganglia
Transcriptome
Heme Oxygenase-1
Oxidative stress
Penis
Zdroj: International Journal of Molecular Sciences, Vol 15, Iss 10, Pp 17204-17220 (2014)
International Journal of Molecular Sciences
Volume 15
Issue 10
Pages 17204-17220
ISSN: 1422-0067
Popis: 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.
Databáze: OpenAIRE
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