Effect of hyaluronic acid on urine nerve growth factor in cyclophosphamide‐induced cystitis

Ho, Dong-Ru; Cheng, Chen-Li; Lin, Wei‐Yu; Chang, Pey‐Jium; Huang, Yun-Chin

doi:10.1111/j.1442-2042.2011.02779.x

Cited by 10 publications

(12 citation statements)

References 38 publications

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“…Systemic treatment of rats with this experimental cystitis model, with an NGF sequestering molecule, has been shown to reduce the bladder overactivity that develops . Another study that reported a significant increase in NGF production, after cyclophosphamide ‐induced cystitis in female rats, showed this was also associated with a decreased intercontraction interval . Once hyaluronic acid was administered intravesically, this significantly reduced the urinary NGF levels and increased the intercontraction interval.…”

Section: Tissue Ngf Levels: Animal and Human Studiesmentioning

confidence: 90%

Nerve growth factor (NGF): a potential urinary biomarker for overactive bladder syndrome (OAB)?

et al. 2013

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The search for a biomarker in overactive bladder syndrome (OAB) is an emerging field of interest, as bladder dysfunction is a common complaint that causes significant morbidity. A biomarker may give us insight as a diagnostic tool, and also inform us about how severe the condition is, how it may progress and how it may best be treated. The protein of interest here is nerve growth factor (NGF) and it has been shown to be a dynamic molecule in the bladder of patients with OAB. Urinary levels have been seen to rise in patients with OAB and fall in those who respond to treatment. However, there have also been many studies that examine this trend in numerous other conditions, e.g. interstitial cystitis, bladder outflow obstruction, renal stone disease and patients with neurological impairment after stroke. As a result the specificity of this as a potential urinary biomarker for OAB is questioned. This is a review of published studies, which discusses the pros and cons of NGF as a potential urinary biomarker. The evidence is examined and the studies are summarised together in a Table. Questions remain about the reliability, practicality and specificity of NGF as a biomarker for OAB. These questions need to be addressed by further studies that could clarify the points raised. Objective• To review the current literature on the use of urinary nerve growth factor (NGF) as a potential biomarker for overactive bladder syndrome (OAB). Method• A comprehensive electronic literature search was conducted using the PubMed database to identify publications relating to urinary NGF. Results• There are a growing number of publications that have measured urinary NGF levels in different types of bladder dysfunction. These range from OAB, bladder pain syndrome, idiopathic and neurogenic detrusor overactivity, bladder oversensitivity and bladder outflow obstruction. Urinary NGF levels do appear to be raised in these pathological states when compared with healthy control samples.• In patients with OAB, these raised urinary NGF levels appear to also reduce after successful treatment with antimuscarinics and botulinum toxin A, which indicates a potential use in monitoring responses to treatment. • However, raised levels are not limited to OAB, which questions its specificity.• Urinary NGF measurements are performed with an enzyme-linked immunosorbent assay using polyclonal antibodies to NGF. The technique requires standardisation, and the different antibodies to NGF require validating.• Also a definition of what is the 'normal' range of NGF in urine is still required before it can be used as a diagnostic and prognostic tool. Conclusions• Whilst the evidence for an increased urinary NGF in OAB appears convincing, many questions about its validity remain including: specificity, sensitivity, cost-and time-effectiveness. • Many criteria for what constitutes a biomarker still need to be evaluated and met before this molecule can be considered for this role. 372

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Section: Tissue Ngf Levels: Animal and Human Studiesmentioning

confidence: 90%

Nerve growth factor (NGF): a potential urinary biomarker for overactive bladder syndrome (OAB)?

et al. 2013

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“…Cystometry was carried out as described previously . The rats were prohibited from drinking water 12 h before CMG, and their bladders were emptied before CMG.…”

Section: Methodsmentioning

confidence: 99%

Interleukin‐6 levels in female rats with protamine sulfate‐induced chronic cystitis treated with hyaluronic acid

Yao

Lin

et al. 2013

Int J of Urology

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Abbreviations & Acronyms BC = bladder capacity BP = base pressure BPS = bladder pain syndrome CMG = cystometrogram ELISA = enzyme-linked immunosorbent assay GAG = glycosaminoglycan GAPDH = glyceraldehydes-3-phosphate dehydrogenase HA = hyaluronic acid IC = interstitial cystitis ICI = intercontraction intervals IL-6 = interleukin-6 mRNA = messenger ribonucleic acid NS = normal saline PP = peak pressure PS = protamine sulfate RNA = ribonucleic acid RT-PCR = reverse transcription polymerase chain reaction RV = residual volume Objectives: To measure interleukin-6 levels in a protamine sulfate-induced chronic cystitis rat model treated with hyaluronic acid, and to study the correlation among interleukin-6, bladder inflammatory degree and voiding frequency. Methods: A chronic cystitis model was created in female rats by using long-term intermittent intravesical protamine sulfate (0.5 mL, 30 mg/mL). Then, hyaluronic acid (0.5 mL, 0.8 mg/mL) was also instilled intravesically in the rats. Interleukin-6 levels were analyzed with immunohistochemistry, real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was carried out to examine bladder inflammatory degree based on a four-point scoring system (from 0 -none to 3 -severe). Voiding patterns were investigated by cystometrography. Results: According to cystometrography, protamine sulfate-induced rats had significantly shorter intercontraction intervals and less bladder capacity (P < 0.001). The bladder tissue of the rats showed severe chronic inflammation. Immunohistochemistry, reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay showed significantly higher expression of interleukin-6 (P < 0.001). After intravesical administration of hyaluronic acid, both intercontraction intervals and bladder capacity increased significantly (P < 0.001), whereas both bladder inflammatory degree and interleukin-6 levels decreased significantly (P < 0.001). Furthermore, there was a strong correlation between interleukin-6 levels and inflammatory degree (r = 0.727, P < 0.001), and also between interleukin-6 levels and voiding frequency (r = -0.761, P < 0.001). Conclusions: Intravesical administration of hyaluronic acid decreases interleukin-6 levels, as well as the severity of bladder inflammation and voiding frequency in a rat model of chronic cystitis. Interleukin-6 levels closely correlate with the inflammatory degree and voiding frequency. Thus, they can be regarded as an assessment measure of therapeutic impact.

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“…Important components of the GAG layer include chondroitin sulfate, hyaluronic acid, heparin sulfate, dermatan sulfate, and keratin sulfate (135), and some agents with GAG-like properties, such as sodium hyaluronate, heparin, and pentosan polysulfate, have been admin-istered intravesically to IC/BPS patients with variable results (87,208,233). In rats, hyaluronic acid was shown to reduce NGF production and bladder overactivity in a cyclophosphamide (CYP)-induced cystitis rat model (133).…”

Section: Treatments Targeting the Mucosamentioning

confidence: 99%

Urothelial Signaling

Birder

Andersson

2013

Physiological Reviews

399

362

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The urothelium, which lines the inner surface of the renal pelvis, the ureters, and the urinary bladder, not only forms a high-resistance barrier to ion, solute and water flux, and pathogens, but also functions as an integral part of a sensory web which receives, amplifies, and transmits information about its external milieu. Urothelial cells have the ability to sense changes in their extracellular environment, and respond to chemical, mechanical and thermal stimuli by releasing various factors such as ATP, nitric oxide, and acetylcholine. They express a variety of receptors and ion channels, including P2X3 purinergic receptors, nicotinic and muscarinic receptors, and TRP channels, which all have been implicated in urothelial-neuronal interactions, and involved in signals that via components in the underlying lamina propria, such as interstitial cells, can be amplified and conveyed to nerves, detrusor muscle cells, and ultimately the central nervous system. The specialized anatomy of the urothelium and underlying structures, and the possible communication mechanisms from urothelial cells to various cell types within the bladder wall are described. Changes in the urothelium/ lamina propria ("mucosa") produced by different bladder disorders are discussed, as well as the mucosa as a target for therapeutic interventions.

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Effect of hyaluronic acid on urine nerve growth factor in cyclophosphamide‐induced cystitis

Cited by 10 publications

References 38 publications

Nerve growth factor (NGF): a potential urinary biomarker for overactive bladder syndrome (OAB)?

Nerve growth factor (NGF): a potential urinary biomarker for overactive bladder syndrome (OAB)?

Interleukin‐6 levels in female rats with protamine sulfate‐induced chronic cystitis treated with hyaluronic acid

Urothelial Signaling

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