Urinary nerve growth factor and a variable solifenacin dosage in patients with an overactive bladder

Çiftçi, Seyfettin; Özkürkçügil, Cüneyd; Yılmaz, Hasan; Üstüner, Murat; Yavuz, Ufuk; Yuksekkaya, Mustafa; Çekmen, Mustafa

doi:10.1007/s00192-015-2825-3

Cited by 9 publications

(7 citation statements)

References 18 publications

(30 reference statements)

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“…and ). NGF is reportedly one of robust biomarkers for overactive bladder (OAB) because of its high concentration in the patients' urine . The expression of P2X2 and TRPA1 receptors was also examined in this study because these receptors that are predominantly expressed in C‐fiber afferent pathways are shown to contribute to afferent sensitization, which has been implicated as a pathophysiological mechanism in OAB and/or bladder inflammation .…”

Section: Discussionmentioning

confidence: 99%

Effects of Estrogen Receptor β Stimulation in a Rat Model of Non‐Bacterial Prostatic Inflammation

et al. 2017

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BACKGROUND There is increasing evidence showing that chronic non-bacterial prostatic inflammation is involved in the pathogenesis of benign prostatic hyperplasia (BPH) and male lower urinary tract symptoms (LUTS). It has also been reported that estrogen receptor β (ERβ) could have an immunoprotective role in prostatic tissue. Therefore, we investigated the effect of ERβ-activation on not only prostatic inflammation, but also bladder overactive conditions in a rat model with nonbacterial prostatic inflammation. METHODS Male Sprague-Dawley rats (8 weeks, n = 15) were divided into three groups: sham-saline group (n = 5), formalin-vehicle group (n = 5), and formalin-treatment group (n = 5). The sham-saline group had sham operation and 50 μl normal saline injected into each ventral lobe of the prostate. The formalin-vehicle group had 50 μl 5% formalin injection into bilateral ventral lobes of the prostate. The formalin-treatment group was treated with 3α-Adiol (a selective ERβ agonist precursor) at a dose of 3 mg/kg daily from 2 days before induction of prostatic inflammation, whereas formalin-vehicle rats received vehicle (olive oil). In each group, conscious cystometry was performed on day 28 after intraprostatic formalin injection or sham treatment. After cystometry, the bladder and prostate were harvested for evaluation of mRNA expression and histological analysis. RESULTS In cystometric investigation, the mean number of non-voiding contractions was significantly greater and voiding intervals were significantly shorter in formalin-vehicle rats than those in sham-saline rats (P < 0.05). In RT-qPCR analysis, mRNA expression of NGF, P2X2, and TRPA1 receptors was significantly increased in the bladder mucosa, and mRNA expression of TNF-α, iNOS and COX2 in the ventral lobes of prostate was significantly increased in formalin-vehicle rats compared with sham-saline rats (P < 0.05). In addition, relative mRNA expression ratio of ERβ to ERα (ERβ/ERα) in the ventral lobes of prostate was significantly decreased in formalin-vehicle rats compared with sham-saline rats (P < 0.05). These changes were ameliorated by 3α-Adiol administration in formalin-treatment rats. CONCLUSIONS These results indicate that ERβ activation by 3α-Adiol administration, which normalized the ERβ/ERα expression ratio in the prostate, can improve not only prostatic inflammation, but also bladder overactivity. Therefore, ERβ agonists might be useful for treating irritative bladder symptoms in patients with symptomatic BPH associated with prostatic inflammation.

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Section: Discussionmentioning

confidence: 99%

Effects of Estrogen Receptor β Stimulation in a Rat Model of Non‐Bacterial Prostatic Inflammation

et al. 2017

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“…Previous studies have indicated that luteolin is a substrate for tyrosinase [ 15 ], and the biological and biochemical activities of luteolin may therefore be associated with the inhibition of tyrosine kinase. Solifenacin is now used clinically to improve overactive bladder by antagonizing the muscarinic receptor [ 25 , 26 ]. Due to having different targets, luteolin and solifenacin may have potential pharmacological synergy in the treatment of DCP.…”

Section: Introductionmentioning

confidence: 99%

Combination of Luteolin and Solifenacin Improves Urinary Dysfunction Induced by Diabetic Cystopathy in Rats

et al. 2018

Med Sci Monit

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BackgroundThe purpose of the present study was to assess the effect of luteolin and solifenacin on diabetic cystopathy (DCP) and to investigate the mechanism of action. A novel link between the overexpression of c-Kit in the bladder and voiding dysfunction was identified in rats with DCP.Material/MethodsA rat model of DCP was successfully established by intraperitoneal injection of streptozotocin and a diet high in glucose and lipids, and animals were treated with luteolin and solifenacin. The effect of luteolin and solifenacin on urinary dysfunction in DCP rats was investigated by assessing bladder pressure and performing a volume test. The protein levels of c-Kit, stem cell factor (SCF), p110, and phosphorylated p110 in the bladder were detected by Western blot analysis and immunohistochemical staining.ResultsIn DCP rats, the protein levels of c-Kit, SCF and phosphorylated p110 in the bladder were significantly increased. However, oral treatment of DCP rats with luteolin combined with solifenacin resulted in effective improvement of overactive bladder and reduced the protein expression of c-Kit, SCF, and phosphorylated p110. Moreover, the effect of luteolin combined with solifenacin on maximum voiding pressure and residual urine volume was improved compared to that of luteolin alone.ConclusionsLuteolin improved overactive bladder in DCP rats, which may be due to SCF/c-kit inhibition, as well as the downregulation of the phosphoinositide-3 kinase signaling pathway. Moreover, solifenacin enhanced the potential pharmacological effect of luteolin in the treatment of DCP.

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“…Several groups have now confirmed the pathogenic role of NGF in NLUTD either by direct antibody‐mediated neutralization of NGF action or by the blockade of NGF expression so that its neutralization attenuates detrusor hyperreflexia in spinal cord injured animals 12,13 . Some authors demonstrated increased NGF levels in patients with idiopathic detrusor overactivity and its reduction as a result of the anticholinergic therapy 13‐16 . The clinical changes of NGF levels in neurogenic bladder patients are less explored 5,7 ; the same applies to the role of BDNF 17‐19 …”

Section: Discussionmentioning

confidence: 99%

Impact of intradetrusor botulinum toxin A injections on serum and urinary concentrations of nerve growth factor and brain‐derived neurotrophic factor in patients with multiple sclerosis and neurogenic detrusor overactivity

Филиппова

Баженов

Ziryanov

et al. 2020

Neurourology and Urodynamics

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Aims: To evaluate the practical relevance of changes in serum and urinary neurotrophins levels in patients with multiple sclerosis (MS) and neurogenic lower urinary tract dysfunction (NLUTD) after intradetrusor injections of botulinum toxin A (BoNTA). Methods: The study included 36 patients with MS and NLUTD and 20 controls. The patients with NLUTD received intradetrusor injection of BoNTA (200 U). The nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels were measured in serum and urine at baseline and then at 1, 3, and 6 months by enzyme-linked immunosorbent assay. Urinary NGF and BDNF were normalized to creatinine (NGF/Cr, BDNF/Cr). Patients' assessment included urodynamic examination and Neurogenic Bladder Symptom Score (NBSS). Results: After BoNTA injections, no significant changes were observed in the serum NGF and BDNF or the urinary BDNF/Cr. The urinary NGF/Cr was significantly higher in MS patients (1.23 ± 0.34) at baseline compared with controls (0.084 ± 0.02; p = .021). The urinary NGF/Cr decreased to 0.51 ± 0.12 (p = .001) and 0.53 ± 0.32 (p = .005) at 1 and 3 months, increasing to 1.12 ± 0.49 (p = .003) at 6 months. The urinary NGF/Cr level at baseline demonstrated a low diagnostic accuracy in predicting a better response to the BoNTA treatment (area under the curve = 0.661; p = .047) and no correlation with the urodynamic parameters. Conclusions: The urinary NGF/Cr at baseline or its reduction at the first month following treatment does not serve as a predictor for the response to the BoNTA injections or for urodynamic changes.

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Urinary nerve growth factor and a variable solifenacin dosage in patients with an overactive bladder

Abstract: Our results suggest that urinary NGF could be a potential biomarker for monitoring the treatment of symptoms in OAB patients who are treated with solifenacin.

Cited by 9 publications

References 18 publications

Effects of Estrogen Receptor β Stimulation in a Rat Model of Non‐Bacterial Prostatic Inflammation

Effects of Estrogen Receptor β Stimulation in a Rat Model of Non‐Bacterial Prostatic Inflammation

Combination of Luteolin and Solifenacin Improves Urinary Dysfunction Induced by Diabetic Cystopathy in Rats

Impact of intradetrusor botulinum toxin A injections on serum and urinary concentrations of nerve growth factor and brain‐derived neurotrophic factor in patients with multiple sclerosis and neurogenic detrusor overactivity

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