prostaglandin-d2 and Cystitis

Inflammation of the urinary bladder may cause burdensome pain also called bladder pain syndrome (BPS). A limitation in understanding BPS pathophysiology is the lack of appropriate preclinical model. Previously published clinical and preclinical studies revealed positive impact of Cernitin™ on pain relief in chronic prostatitis. The objective of this study was to evaluate the effects of Cernitin™ on induced inflammation of the urinary bladder in rats. We also sought to identify biomarkers which might play a role in the management of BPS.. Cystitis was induced by injection of cyclophosphamide (CYP) in female rats. Thereafter, animals were randomly divided into four treatment groups and two control groups. Evaluation of pain scores was assessed by von Frey assay. Expression of pain- and pro-inflammatory biomarkers was determined by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry.. Treatments with Cernitin™ displayed significant anti-nociceptive effects on CYP-induced visceral pain (. Cernitin™ components reduced pain score and inflammatory marker COX-2. Our findings suggest a potential therapeutic role for Cernitin™ in the management of BPS.

Topics: Animals; Biomarkers; Cyclooxygenase 2; Cyclophosphamide; Cystitis; Female; Male; Pain; Prostaglandin D2; Rats

To investigate whether an endogenous prostaglandin (PG) D2 metabolite, 15-deoxy-Delta12,14-PGJ2 (15d-PGJ2), can attenuate cyclophosphamide (CYP)-induced cystitis in the rat.. Male Sprague-Dawley rats received a single intraperitoneal injection of CYP (200 mg/kg). In a separate group of animals, 15d-PGJ2 (10 and 100 microg/kg intraperitoneal bolus 10 minutes before and 24 hours after CYP injection) or a selective inducible nitric oxide synthase (iNOS) inhibitor, N-(3-(aminomethyl)benzyl)acetamidine ([1400W] 10 mg/kg intraperitoneal bolus 10 minutes before and 12 and 24 hours after CYP injection), was administered. At 48 hours after CYP injection, the rats were killed, and tissues were removed for evaluation of cystitis.. CYP injection resulted in severe cystitis. 15d-PGJ2, as well as 1400W, significantly reduced the increase in plasma protein extravasation (Evans blue dye method), iNOS enzymatic activity, urinary excretion of nitric oxide metabolites, and myeloperoxidase activity in the bladder caused by CYP. Moreover, 15d-PGJ2 significantly decreased the cytokine interleukin-1beta in the bladder. In addition, 15d-PGJ2 significantly reduced the degree of CYP-induced bladder tissue damage and increase in immunohistochemical staining for iNOS in the bladder.. These results indicate that 15d-PGJ2 can attenuate the development of CYP-induced cystitis by suppression of cytokine production and iNOS induction. Thus, treatment with cyclopentenone prostaglandins such as 15d-PGJ2 may be effective against CYP-induced cystitis.

Topics: Animals; Cyclophosphamide; Cystitis; Immunologic Factors; Interleukin-1; Male; Nitric Oxide Synthase Type II; Prostaglandin D2; Rats; Rats, Sprague-Dawley

The purpose of this study was to determine the role of cyclooxygenase-2 (COX-2) and its metabolites in lower urinary tract function after induction of acute (4 h), intermediate (48 h), or chronic (10 day) cyclophosphamide (CYP)-induced cystitis. Bladders were harvested from euthanized female rats for analyses. Conscious cystometry was used to assess the effects of a COX-2-specific inhibitor, 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl2(5H)-furanone (DFU, 5 mg/kg sc), a disubstituted furanone, in CYP-induced cystitis. COX-2 mRNA was increased in inflamed bladders after acute (12-fold) and chronic (9-fold) treatment. COX-2 protein expression in inflamed bladders paralleled COX-2 mRNA expression. Prostaglandin D2-methoxime expression in the bladder was significantly (P < or = 0.01) increased in acute (3-fold) and chronic (5.5-fold) cystitis. Prostaglandin E2 was significantly (P < or = 0.01) increased (2-fold) in the bladder with intermediate (1.7-fold) and chronic (2.6-fold) cystitis. COX-2-immunoreactive cell profiles were distributed throughout the inflamed bladder and coexpressed histamine immunoreactivity. Conscious cystometry in rats treated with CYP + DFU showed increased micturition intervals 4 and 48 h after CYP treatment and decreased intravesical pressures during filling and micturition compared with rats treated with CYP + vehicle. These studies suggest an involvement of urinary bladder COX-2 and its metabolites in altered micturition reflexes with CYP-induced cystitis.

Topics: Animals; Blotting, Western; Cyclooxygenase 2; Cyclophosphamide; Cystitis; Dinoprostone; Drug Administration Schedule; Female; Furans; Gene Expression Regulation; Immunoenzyme Techniques; Immunohistochemistry; Isoenzymes; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Prostaglandins, Synthetic; Rats; Rats, Wistar; RNA, Messenger; Urinary Bladder; Urination