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

Lv, Yisong; Yao, Yousheng; Lin, Mingen; Lu, Rong; Deng, Bi-hua; Huang, Jian; Hao, Wei-Ping

doi:10.1111/iju.12090

Cited by 20 publications

(32 citation statements)

References 29 publications

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“…In the present study, levels of IL‐1β and TNF‐α, which are usually increased in acute inflammation, did not change; whereas the level of IL‐6 increased along with the severity of inflammation. The present results were similar to those of some experimental or clinical trials in BPS . IL‐6, as an important factor in acute and chronic inflammation, has a strong relationship with bladder fibrosis and detrusor overactivity, and can be used as an objective indicator for the inflammatory process of the BPS model and an effective assessment for therapeutic impact …”

Section: Discussionsupporting

confidence: 89%

“…In the HAase‐treated groups, a PE‐50 catheter (Clay Adams, Parsippany, NJ, USA) was inserted into the bladder through the urethra to empty the bladder, and then 0.5 mL HAase (1 mg/mL or 4 mg/mL) was infused intravesically for 30 min. In the HA‐treated group, 6 h after HAase (1 mg/mL) instillation, the rats were intravesically instilled with 0.5 mL of HA (0.8 mg/mL, Bioniche, Belleville, Ontario, Canada) at each time . In the control group, 0.5 mL saline was infused following the same procedure.…”

Section: Methodsmentioning

confidence: 99%

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Intravesical hyaluronidase causes chronic cystitis in a rat model: A potential model of bladder pain syndrome/interstitial cystitis

Yao

et al. 2013

Int J of Urology

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Abbreviations & Acronyms BC = bladder capacity BP = base pressure BPS = bladder pain syndrome BW-A = bodyweight after instillation BW-B = bodyweight before instillation CMG = cystometry CYP = cyclophosphamide GAG = glycosaminoglycan GAPDH = glyceraldehydes-3-phosphate dehydrogenase HA = hyaluronic acid HAase = hyaluronidase HHAase = high-dose hyaluronidase IC = interstitial cystitis ICAM-1 = intercellular adhesion molecule-1 ICI = intercontraction intervals IL = interleukin LHAase = low-dose hyaluronidase mRNA = messenger ribonucleic acid PP = peak pressure PS = protamine sulfate RNA = ribonucleic acid RT-PCR = reverse transcription polymerase chain reaction RV = residual volume TNF = tumor necrosis factor UPIII = uroplakin III Zo-1 = zonula occludens-1 Objectives: To determine whether a potential rat model of bladder pain syndrome could be developed through long-term intermittent intravesical hyaluronidase. Methods: A total of 64 female Sprague-Dawley rats were divided into a control group, a low-dose hyaluronidase (1 mg/mL) group, a high-dose hyaluronidase (4 mg/mL) group and a hyaluronic acid-treated group. Hyaluronidase was given intravesically three times a week for 1 month. Hyaluronic acid (0.5 mL, 0.8 mg/mL) was introduced intravesically to hyaluronidasetreated rats' bladders. Histological changes, cystometry, nociceptive behaviors, and messenger ribonucleic acid levels of inflammatory factors were evaluated and compared between groups. Results: All hyaluronidase-treated rats showed chronic inflammation and fibrosis, increased and activated mast cells, thinned bladder epithelium with abnormal expressions of uroplakin III and zonula occluden-1, and increased levels of interleukin-6 and intercellular adhesion molecule-1 messenger ribonucleic acid. However, the inflammatory score and levels of interleukin-6 and intercellular adhesion molecule-1 were more significant in the high-dose hyaluronidase group than in the low-dose hyaluronidase group (P < 0.01). Furthermore, hyaluronidase-treated rats showed markedly decreased intercontraction intervals, bladder capacity and increased sensitivity to pain compared with controls (P < 0.01). Hyaluronic acid treatment significantly decreased the inflammatory level, number of mast cells, sensitivity to pain, levels of interleukin-6 and intercellular adhesion molecule-1, and increased intercontraction intervals and bladder capacity (P < 0.01). Conclusions: Long-term intermittent intravesical hyaluronidase could develop a severe chronic cystitis with diffused fibrosis accompanied by altered histology and bladder function. This chronic cystitis rat model can resemble the clinical and histopathological features of human bladder pain syndrome, and might be a potential valuable model for investigation of this troublesome disease.

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Section: Discussionsupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Intravesical hyaluronidase causes chronic cystitis in a rat model: A potential model of bladder pain syndrome/interstitial cystitis

Yao

et al. 2013

Int J of Urology

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“…Lv et al . recently reported that in a protamine sulphate intermittent cystitis model, IL‐6 bladder expression has a positive correlation with histological inflammation grade, and a negative correlation with the bladder intercontraction interval measured at cystometry . Both correlations were influenced by intravesical administrations of HA: reduction of IL‐6 expression with lower inflammatory grade, longer voiding frequency and higher bladder capacity.…”

Section: Methodsmentioning

confidence: 93%

“…Finally, the GAG effect on the inflammatory process was also investigated though urinary markers . Lv et al .…”

Section: Methodsmentioning

confidence: 99%

Restoring the glycosaminoglycans layer in recurrent cystitis: Experimental and clinical foundations

et al. 2014

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Abbreviations & Acronyms 5-ASA = 5-aminosalicylic bwk = biweekly CS = chondroitin sulphate GAG = glycosaminoglycans HA = hyaluronic acid IL-6 = interleukin-6 LE = evidence level LPS = lipopolysaccharide NGF = nerve growth factor PS = protamine sulfate PSP = pentosanpolysulphate RCT = randomized controlled trial rUTI = recurrent urinary tract infections SAGE = semi-synthetic glycosaminoglycans ethers sNOCC = N-sulphonato-N,O -carboxymethylchitosan UTI = urinary tract infections Abstract: Restoring the bladder glycosaminoglycans layer has recently been introduced as prophylactic treatment for recurrent urinary tract infections. Herein, we analyze the latest main clinical and experimental studies to support this therapeutic option. An electronic research was carried out in the most common databases in order to identify any published studies. Retrieved studies were categorized as experimental or clinical according to their setting. For the clinical studies, the evidence level was assigned. A total of 13 laboratory studies showed how bladder glycosaminoglycans instillations act: attenuation of the inflammation process, reduction of bladder contraction amplitude and frequency, reduction of epithelium damage, and lower bacterial growth in urine and tissue samples. Likewise, two randomized clinical trials with grade 2 evidence level and two case series with grade 4 evidence level reported glycosaminoglycans as an alternative to reduce episodes and to prolong recurrence time in patients with recurrent urinary tract infections. At least 12 months of follow up was completed. No serious adverse events were reported. Compared with a placebo, in one randomized study a significantly higher maximum cystometric capacity was obtained, whereas in the other study a significant increase in quality of life scores was reported too. An improvement in the urinary symptoms score was reported by the two randomized trials. Although the clinical use of glycosaminoglycans replacement therapy for recurrent urinary tract infections is supported by a small number of clinical studies with different evidence levels, the laboratory studies show that glycosaminoglycans could have a protective role against inflammatory factors, supporting the idea "to restore the glycosaminoglycans bladder layer to prevent chronic disease course".

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“…In the present study, Lv et al . investigated the correlation between interleukin (IL)‐6 levels and the inflammatory degree, as well as the voiding frequency in protamine sulfate‐induced chronic cystitis rats with or without treatment of hyaluronic acid . They concluded that tissue levels of IL‐6 might be an effective assessment of the therapeutic impact of interstitial cystitis/bladder pain syndrome (IC/PBS).…”

mentioning

confidence: 99%

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

Saito

2013

Int J of Urology

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

Cited by 20 publications

References 29 publications

Intravesical hyaluronidase causes chronic cystitis in a rat model: A potential model of bladder pain syndrome/interstitial cystitis

Intravesical hyaluronidase causes chronic cystitis in a rat model: A potential model of bladder pain syndrome/interstitial cystitis

Restoring the glycosaminoglycans layer in recurrent cystitis: Experimental and clinical foundations

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

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