Relevance of the cyclophosphamide-induced cystitis model for pharmacological studies targeting inflammation and pain of the bladder

Augé, Céline; Chene, Gerald; Dubourdeau, Marc; Desoubzdanne, Denis; Corman, B.; Palea, Stéfano; Lluel, Philippe; Vergnolle, Nathalie; Coelho, Anne-Marie

doi:10.1016/j.ejphar.2013.03.008

Cited by 68 publications

(72 citation statements)

References 44 publications

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“…After the administration, the bladder wall displayed macroscopic oedema and subcapsular vasculature were congested ( Supplementary Fig. 6), which is consistent with a previous report 20 . Immunohistochemistry results showed that Pirt-ir and P2X3-ir occurred predominantly in the nerve fibres of the bladder (Fig.…”

Section: Resultssupporting

confidence: 81%

“…Bladder inflammation induced by CYP in rats sensitizes and increases P2X3 receptor function 30 . CYP-induced cystitis is a frequently used animal model 19,20,30,31 . CYP is an antineoplastic agent, and it is metabolized to acrolein by the liver 32,33 .…”

Section: Discussionmentioning

confidence: 99%

“…Saline at 37°C was infused at a rate of 0.1 ml min À 1 . For the Pirt N14 peptide study, 200 ml of the peptide solution with corresponding concentration (20, 40 or 60 mg kg À 1 ) was injected into the bladder cavity through the three-way stopcock. This volume of peptide solution swept away the saline in the catheter and bladder cavity and about 90 ml (WT or Pirt À / À mice) or 50 ml (CYP-treated mice) peptide solution was left in the cavity.…”

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confidence: 99%

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Pirt reduces bladder overactivity by inhibiting purinergic receptor P2X3

et al. 2015

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Pirt is a transmembrane protein predominantly expressed in peripheral neurons. However, the physiological and pathological roles of Pirt in hollow viscus are largely unknown. Here we show that Pirt deficiency in mice causes bladder overactivity. The density of a,b-meATP-induced currents is significantly reinforced in Pirt-deficient dorsal root ganglion (DRG) neurons. Pirt and P2X3 receptor co-localize in bladder nerve fibres and heterologous Pirt expression significantly reduces P2X3-mediated currents. Pirt interacts with P2X3 through the N-terminal 14 amino-acid residues. TAT-conjugated Pirt N14 peptide (Pirt N14 ) is sufficient to inhibit P2X3 activation in bladder DRG neurons and to alleviate bladder overactivity in Pirt À / À mice. Pirt expression is decreased in the bladder of cyclophosphamide (CYP)-treated mice, a commonly used model of bladder overactivity. Importantly, Pirt N14 administration reduces the frequency of bladder voiding and restores the voided volume of CYP-treated mice. Therefore, our results demonstrate that Pirt is an endogenous regulator of P2X3 in bladder function.

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Section: Resultssupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Pirt reduces bladder overactivity by inhibiting purinergic receptor P2X3

et al. 2015

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“…Interestingly, acute inflammatory insults have the ability to impact its primary functions of storing large volumes of urine at low pressures, in protecting the kidneys from pressure-related damage, and efficiently emptying to completion under appropriate social conditions (6). Cyclophosphamide (CPX) 2 -induced urinary bladder inflammation is an established experimental model for bladder pain syndrome (2,(7)(8)(9). CPX is a chemotherapeutic agent that metabolizes to acrolein and accumulates in the bladder of patients (10 -14).…”

mentioning

confidence: 99%

Inflammation and Pyroptosis Mediate Muscle Expansion in an Interleukin-1β (IL-1β)-dependent Manner

Haldar

Dru

Choudhury

et al. 2015

Journal of Biological Chemistry

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Background: Hyperplasia is a common phenomenon in inflamed muscle. Results: IL-1␤ secreted associated with pyroptotic cell death mediate IGF1-dependent detrusor expansion. Conclusion: Bladder muscle hyperplasia resulting from NLRP3 inflammatory cascade can be attenuated by neutralization of IL-1␤ and IGF1. Significance: Antagonizing IL-1␤ can have a therapeutic benefit for subjects with muscle hyperplasia resulting from chronic inflammatory diseases.

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“…With minor modifications it is currently widely used experimental tool for investigation of pathogenesis, prevention, and treatment of haemorrhagic cystitis as well as urothelial injury, bladder inflammation, bladder-related pain, and acute and chronic overactive bladder [58, 59, 76, 81, 85, 86]. An immediate effect of cyclophosphamide metabolites is seen as widespread destruction of the urothelium, which is accompanied not only by necrosis but also by apoptosis of urothelial cells, with only a few surviving cells remaining after 24 hours (Figure 3) [78, 87].…”

Section: Experimental Models Of Haemorrhagic Cystitismentioning

confidence: 99%

Cystitis: From Urothelial Cell Biology to Clinical Applications

Lee

Romih

Zupančič

2014

BioMed Research International

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Cystitis is a urinary bladder disease with many causes and symptoms. The severity of cystitis ranges from mild lower abdominal discomfort to life-threatening haemorrhagic cystitis. The course of disease is often chronic or recurrent. Although cystitis represents huge economical and medical burden throughout the world and in many cases treatments are ineffective, the mechanisms of its origin and development as well as measures for effective treatment are still poorly understood. However, many studies have demonstrated that urothelial dysfunction plays a crucial role. In the present review we first discuss fundamental issues of urothelial cell biology, which is the core for comprehension of cystitis. Then we focus on many forms of cystitis, its current treatments, and advances in its research. Additionally we review haemorrhagic cystitis with one of the leading causative agents being chemotherapeutic drug cyclophosphamide and summarise its management strategies. At the end we describe an excellent and widely used animal model of cyclophosphamide induced cystitis, which gives researches the opportunity to get a better insight into the mechanisms involved and possibility to develop new therapy approaches.

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Relevance of the cyclophosphamide-induced cystitis model for pharmacological studies targeting inflammation and pain of the bladder

Cited by 68 publications

References 44 publications

Pirt reduces bladder overactivity by inhibiting purinergic receptor P2X3

Pirt reduces bladder overactivity by inhibiting purinergic receptor P2X3

Inflammation and Pyroptosis Mediate Muscle Expansion in an Interleukin-1β (IL-1β)-dependent Manner

Cystitis: From Urothelial Cell Biology to Clinical Applications

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