Role of oxidative stress in surgical cavernous nerve injury in a rat model

Wang, Hui; Ding, Xiegang; Li, Shiwen; Zheng, Hua; Zheng, Xiaodong; Navin, Shrestha; Li, Lü; Wang, Xinghuan

doi:10.1002/jnr.23545

Cited by 22 publications

(14 citation statements)

References 17 publications

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“…At the cellular level, CN injury results in apoptosis of corporal smooth muscle and endothelium, upregulation of profibrotic cytokines, hypoxia, increased collagen synthesis, and fibrosis within the corpora cavernosa [3][4][5][6]. Molecular conditions underlying these changes involve upregulation of the RhoA-ROCK pathway, dysregulation of growth factor expression, increased oxidative/nitrosative stress, and decreased neuronal nitric oxide (NO) synthase (nNOS) expression in the penile innervation [7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

cAMP‐dependent post‐translational modification of neuronal nitric oxide synthase neuroprotects penile erection in rats

et al. 2017

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Objectives To evaluate nNOS phosphorylation, nNOS uncoupling, and oxidative stress in the penis and major pelvic ganglia (MPG), before and after the administration of the cAMP-dependent protein kinase A (PKA) agonist colforsin in a rat model of bilateral cavernous nerve injury (BCNI) which mimics nerve injury following prostatectomy. Materials and Methods Adult male Sprague–Dawley rats were divided into BCNI and sham groups. Each group included 2 subgroups: vehicle and colforsin (0.1 mg/kg/day i.p.). After 3 days, erectile function (intracavernosal pressure) was measured and penes and MPG were collected for molecular analyses of phospho(P)-nNOS (Ser-1412 and Ser-847), total nNOS, nNOS uncoupling, binding of neuronal nitric oxide synthase (PIN) to nNOS, gp91phox subunit of NADPH oxidase, active caspase 3, PKA catalytic subunit alpha (PKA-Cα) (by Western blot) and oxidative stress (hydrogen peroxide [H2O2] and superoxide by Western blot and microdialysis method). Results Erectile function was decreased 3 days after BCNI and normalized by colforsin. nNOS phosphorylation on both positive (Ser-1412) and negative (Ser-847) regulatory sites, and nNOS uncoupling, were increased after BCNI in the penis and MPG and normalized by colforsin. Hydrogen peroxide and total ROS productions were increased in the penis after BCNI and normalized by colforsin. Protein expression of gp91phox was increased in the MPG after BCNI and was normalized by colforsin treatment. Binding of PIN to nNOS was increased in the penis after BCNI and was normalized by colforsin treatment. Protein expression of active Caspase 3 was increased in the MPG after BCNI and was normalized by colforsin treatment. Protein expression of PKA-Cα was decreased in the penis after BCNI and normalized by colforsin. Conclusion Collectively, BCNI impairs nNOS function in the penis and MPG by mechanisms involving its phosphorylation and uncoupling in association with increased oxidative stress, resulting in erectile dysfunction. PKA activation by colforsin reverses these molecular changes and preserves penile erection in the face of BCNI.

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Section: Introductionmentioning

confidence: 99%

cAMP‐dependent post‐translational modification of neuronal nitric oxide synthase neuroprotects penile erection in rats

et al. 2017

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“…Oxidative stress is one of those major hallmarks, contributing prominently in exacerbating the pathological phenomena happening at the injury site (Wang et al., 2015 ). Following nerve injury, cascades of reactions (i.e., mitochondrial dysfunctions, demyelination, neuroinflammation, and apoptosis (Hussain et al., 2020 )) happen which result in the generation of oxidants that worsen the injury and delay the regenerative processes (Al‐Nimer et al., 2012 ; Areti et al., 2014 ).…”

Section: Resultsmentioning

confidence: 99%

Calotropis procera (leaves) supplementation exerts curative effects on promoting functional recovery in a mouse model of peripheral nerve injury

Zafar

Rasul

Iqbal

et al. 2021

Food Science & Nutrition

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“… 46 , 47 Peripheral nerve injury induces the production of reactive oxygen species and nitric oxide in axotomized neurons; additionally, Schwann cells and macrophages express pro-inflammatory molecules such as interleukin IL-1β, IL-6, IL-12, TNF-α, TGF-β, and in turn contribute to injury of neurons. 48 , 49 Research suggests that blocking oxidative stress can accelerate the repair process and facilitate functional recovery after peripheral nerve injury. 50 , 51 In this research, H 2 O 2 treatment was used to mimic oxidative stress to Schwann cells.…”

Section: Discussionmentioning

confidence: 99%

<p>Ulinastatin Promotes Regeneration of Peripheral Nerves After Sciatic Nerve Injury by Targeting let-7 microRNAs and Enhancing NGF Expression</p>

Zhang

Chen

et al. 2020

DDDT

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Background: Peripheral nerve injury is characterized as a common clinical problem. Ulinastatin (UTI) is a serine protease inhibitor with many biological activities including antiinflammatory and antioxidant effects. Nonetheless, it is unknown whether UTI has a protective effect on peripheral nerve injury. Methods: Thirty rats were divided into the sham operation group, the sciatic nerve injury group (injected with normal saline), and the UTI treatment group (80mg/kg/day for two consecutive weeks). Sciatic nerve function index (SFI) was used to assess the biological functions of the sciatic nerve, and compound muscle action potential (CMAP) was measured by electrophysiology. The expressions of let-7 miRNA members were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Nerve growth factor (NGF), nerve regeneration-related proteins GAP43 and NF200, and myelin formation-related proteins MAG and PMP22 expressions were explored by Western blot. After Schwann cells were transfected with let-7 mimics, pcDNA3.1-NGF, let-7 inhibitors, NGF siRNA and their corresponding controls, 5-ethynyl-2ʹ-deoxyuridine (EdU) assay, and Transwell assays were employed to investigate the proliferation and migration of Schwann cells. H 2 O 2 was utilized to construct oxidative injury to cells, and the contents of MDA, SOD, GSH, and CAT were determined. Results: UTI treatment remarkably increased SFI of the rats and CMAP of sciatic nerve, enhanced nerve regeneration, and myelin regeneration, and raised the production of GAP43, NF200, MAG, and PMP22. Furthermore, it was found that UTI markedly reduced let-7 miRNAs' expressions and increased NGF expression after sciatic nerve injury. The dualluciferase reporter assay validated that let-7 miRNAs targeted NGF, and functional experiments demonstrated that low expression of let-7 miRNAs and NGF overexpression contributed to Schwann cells' proliferation and migration. Additionally, UTI treatment repressed the oxidative stress regulated by let-7/NGF axis. Conclusion: UTI modulates the let-7/NGF axis to inhibit oxidative stress, promote nerve regeneration, and facilitate function recovery after peripheral nerve injury.

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Role of oxidative stress in surgical cavernous nerve injury in a rat model

Cited by 22 publications

References 17 publications

cAMP‐dependent post‐translational modification of neuronal nitric oxide synthase neuroprotects penile erection in rats

cAMP‐dependent post‐translational modification of neuronal nitric oxide synthase neuroprotects penile erection in rats

Calotropis procera (leaves) supplementation exerts curative effects on promoting functional recovery in a mouse model of peripheral nerve injury

<p>Ulinastatin Promotes Regeneration of Peripheral Nerves After Sciatic Nerve Injury by Targeting let-7 microRNAs and Enhancing NGF Expression</p>

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