• Biomolecules & Therapeutics
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• v.3 no.1
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• pp.58-62
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• 1995

We investigated whether nitric oxide (NO) may serve a role in bladder function by immunohistochemical analysis of the distribution of intrinsic NADPH-diaphorase and functional study of isometric tension recordings via a photo-induced adequate nitric oxide (PIANO) generating system using rat bladder. Results suggest that a small number of NADPH-diaphorase-positive perikarya are present within the bladder wall and within adjacent small ganglia. Furthermore, NADPH-diaphorase-positive nerve fibers were observed in the adventitial and muscular layers, subjacent to the urothelium and perivascular fibers. Rat bladder strips precontracted with 3$\mu$M carbachol were reversibly relaxed upon NO generation by UV irradiation. PIANO-mediated relaxation was sensitive to oxygen free radicals. In addition, tissue cGMP levels were increased by the PIANO generating system and elevated cGMP levels were decreased by pretreatment of guanylate cyclase inhibitor, methylene blue. These results indicate that NO may serve a role in modulating bladder tone in the rat.

• Journal of Animal Science and Technology
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• v.54 no.6
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• pp.419-425
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• 2012

The coordinated action of the detrusor muscle cells in the urinary bladder is governed by cell-cell communication through gap junction, consisted of connexin (Cx) molecules. Even though a number of researches have been mostly focused on expressional changes of a few Cx isoforms in clinically dysfunctional condition of the bladder, less attention has been paid for investigation of Cx isoforms present in the bladder. Using real-time PCR analysis, the present study examined Cx isoforms expressing in the male rat bladder during postnatal period. Also, expressional patterns of Cx isoforms were evaluated in the bladder at different postnatal ages. Of a total of 13 Cx isoforms tested in the present study, we were able to detect mRNAs of 6 Cx isoforms in the rat urinary bladder, including Cxs 31, 31.1, 32, 37, 40, and 45. The transcript levels of Cxs 31, 31.1, 37, 40, and 45 were gradually increased from 1 week of age until 25 days of age, followed by transient decreases at 45 days of age. However, abundance of Cx32 transcript was drastically increased at 15 days of age, followed by a sharp drop at 45 days of age. These results indicate that differential expression of Cx isoforms in the bladder during postnatal development would be necessary for maintaining proper function of the bladder. A question remains to be answered if significant decreases of transcript levels of some Cx isoforms at the elderly are associated with age-dependent dysfunction of the bladder.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.2
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• pp.429-433
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• 2005

We investigated the effects of aqueous extract from talc for suppression in the process of cyclophosphamide-induced cystitis in the rat. The weight of urinary bladder was increased in the cyclophosphamide-injected rat compared with normal, but the increase of weight was arrested by intake of talc. More similar results showed in the uric test involving nitrate content and blood cell number and serum analysis involving the content of blood urea nitrogen and uric acid in the talc challenged rat compared with control one. More severe histological changes of urinary bladder such as edema, wall thickness, bleeding, vacuolation in mucosal epithelium were demonstrated in the rat injected with cyclophosphamide compared with normal. Fewer scores of these changes such as edema and bleeding were observed in rats treated with talc. In the immunohistochemical analysis, the expression of inflammatory-related protein examined tended to increase in the urinary bladder of cyclophosphamide-injected rat, especially COX-2 and $TNF-{\alpha}$ in mucosal epithelium and iNOS and $IL-1{\beta}$ in mucosal and muscular layer. The decline of these immunoreation were observed in the talc treated rat, significant decrease of COX-2 was detected in mucosal epithelium and iNOS in submucosal layer. These results suggest that talc may use as a useful therapeutic agent for noninfectious cystitis.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.473-478
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• 2015

To see the inhibitory mechanism of gentamicin in response to electrical field stimulation (EFS) using the rat bladder smooth muscle, atropine or guanethidine was treated but had no effect. Methylsergide, a non-selective 5-$HT_1$, 5-$HT_2$ receptor antagonist was also treated but had on effect. Kinase inhibitors, such as chelerythrine (PKC inhibitor), ML-9 (MLCK inhibitor), or Y27632 (rho kinase inhibitor) were pretreated before gentamicin treatment, but did not have effect. For U73122, a phospholipase C (PLC) inhibitor however, the inhibitory effect to gentamicin was significantly attenuated in all frequencies given by the EFS. Therefore gentamicin induced inhibitory effect on EFS response in rat bladder smooth muscle was not mediated by the activation of adrenergic, cholinergic, or serotonergic receptor. The inhibition of gentamicin might be mediated through the PLC dependent pathway, but not through the PKC, MLCK or rho kinase dependent pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4537-4542
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• 2015

OK-432, a Streptococcus-derived anticancer immunotherapeutic agent, has been applied in clinic for many years and achieved great progress in various cancers. In the present study, we investigated its anticancer effect on bladder cancer through tumor associated macrophages (TAMs). MTS assay validated OK-432 could inhibit proliferation in both T24 and EJ bladder cell lines. OK-432 also induced apoptosis of bladder cancer cells in vitro. Consequently, we demonstrated that OK-432 could suppress the bladder cancer cells migration and invasion by altering the EMT-related factors. Furthermore, using SD rat model, we revealed that OK-432 inhibited tumor growth, suppressed PCNA expression and inhibited metastasis in vivo. Taken together, these findings strongly suggest that OK-432 inhibits cell proliferation and metastasis through inducing macrophages to secret cytokines in bladder cancer.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.4
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• pp.417-424
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• 2020

This study aimed to explore the effects of brain-derived neurotrophic factor (BDNF), produced by engineered immortalized mesenchymal stem cells (imMSC), on lower urinary tract symptoms (LUTS) in a rat model with neurogenic bladder (NB). Forty-eight Sprague-Dawley (SD) rats were randomly divided into the following groups: Sham control, LUTS, LUTS+imMSC (treated with immortalized MSC), and LUTS+BDNF-eMSC (treated with BDNF-expressing MSC) groups. LUTS was induced by a crush injury to the major pelvic ganglion (MPG). Bladder function was tested under anesthesia, and bladder tissue strips were collected thereafter for contractility test and western blot analysis. Western blot results showed that the expression of both Angiopoietin 1 (Ang 1) and platelet-derived growth factor (PDGF) increased with MSC injection. The effect of treatment with BDNF-eMSC on LUTS was also evaluated, and the results were found to be better than those with imMSC (P<0.05). BDNF-eMSC prevented fibrosis in the bladder tissue and significantly reduced caspase-3 levels. In conclusion, high expression of BDNF in vivo resulted in recovery of bladder function and contractility, along with the inhibition of apoptosis in a rat model.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.101-106
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• 2019

Most diabetic patients experience diabetic mellitus (DM) urinary bladder dysfunction. A number of studies evaluate bladder smooth muscle contraction in DM. In this study, we evaluated the change of bladder smooth muscle contraction between normal rats and DM rats. Furthermore, we used pharmacological inhibitors to determine the differences in the signaling pathways between normal and DM rats. Rats in the DM group received an intraperitoneal injection of 65 mg/kg streptozotocin and measured blood glucose level after 14 days to confirm DM. Bladder smooth muscle contraction was induced using acetylcholine (ACh, $10^{-4}M$). The materials such as, atropine (a muscarinic receptor antagonist), U73122 (a phospholipase C inhibitor), DPCPX (an adenosine $A_1$ receptor antagonist), udenafil (a PDE5 inhibitor), prazosin (an ${\alpha}_1$-receptor antagonist), papaverine (a smooth muscle relaxant), verapamil (a calcium channel blocker), and chelerythrine (a protein kinase C inhibitor) were pre-treated in bladder smooth muscle. We found that the DM rats had lower bladder smooth muscle contractility than normal rats. When prazosin, udenafil, verapamil, and U73122 were pre-treated, there were significant differences between normal and DM rats. Taken together, it was concluded that the change of intracellular $Ca^{2+}$ release mediated by PLC/IP3 and PDE5 activity were responsible for decreased bladder smooth muscle contractility in DM rats.

• Korean Journal of Veterinary Pathology
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• v.1 no.2
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• pp.107-118
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• 1997

The anticarcinogenic effects of allyl methyl trisulfide(AMT) and methyl propyl disulfide(MPD) were studied in a 28 weeks rat multi-organ carcinogenesis model. Tumor incidence rate was decreased by AMT or MPD treatment comparing with the positive control. AMT treatment significantly decreased the incidence of neoplastic and preneoplastic lesions in the kidney thyroid gland urinary bladder alimentary tract lung and Zymbal's gland. MPD also inhibited incidence of noplastic and preneoplastic lesions in the liver kidney urinary bladder alimentary tract lung and Zymbal's gland but increased that in the thyroid gland. GST-p positive foci in the liver were slightly decreased by AMT or MPD. There was no significant histopathological lesions in AMT or MPD treated group without pretreatment of carcinogens.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.3
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• pp.143-147
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• 2011

Defensins, cysteine-rich cationic polypeptides released from neutrophils, are known to have powerful antimicrobial properties. In this study, we sacrificed 30 rats to investigate the effects of ${\alpha}$-defensin 1 on detrusor muscle contractions in isolated rat bladder. From the experiments we found relaxing effects of ${\alpha}$-defensin 1 on the contractions induced by phenylephrine (PE) but not by bethanechol (BCh) in the detrusor smooth muscles. To determine the mechanisms of the effects of ${\alpha}$-defensin 1, the changes of effects on PE-induced contraction by ${\alpha}$-defensin 1 pretreatment were observed after pretreatment of Rho kinase inhibitor (Y-27632), protein kinase C (PKC) inhibitor (Calphostin C), potent activator of PKC (PDBu; phorbol 12,13-dibutyrate), and NF-${\kappa}B$ inhibitors (PDTC; pyrrolidinedithiocarbamate and sulfasalazine). The contractile responses of PE ($10^{-9}{\sim}10^{-4}$ M) were significantly decreased in some concentrations of ${\alpha}$-defensin 1 ($5{\times}10^{-9}$ and $5{\times}10^{-8}$ M). When strips were pretreated with NF-kB inhibitors (PDTC and sulfasalazine; $10^{-7}{\sim}10^{-6}$ M), the relaxing responses by ${\alpha}$-defensin 1 pretreatment were disappeared. The present study demonstrated that ${\alpha}$-defensin 1 has relaxing effects on the contractions of rat detrusor muscles, through NF-${\kappa}B$ pathway. Further studies in vivo are required to clarify whether ${\alpha}$-defensin 1 might be clinically related with bladder dysfunction by inflammation process.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.2
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• pp.112-118
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• 2020

This study was undertaken to examine the effects and to investigate the relevant mechanisms of overexpressing stromal cell-derived factor-1 (SDF-1) produced by engineered mesenchymal stem cells, in a neurogenic bladder (NB) rat model. Sprague-Dawley (SD) rats (N=48) were randomly divided into 4 groups comprising 12 rats each: control group, Injury group, Injury+imMSC group, and Injury+SDF-1 eMSC group. Rats in the Injury+imMSC group were treated with imMSCs, whereas the Injury+SDF-1 eMSC group were administered SDF-1 eMSCs. After 4-weeks therapy, the bladder and pelvic nerve (PN) tissues were examined by subjecting to Masson's trichrome staining and immunofluorescence. Administration of SDF-1 eMSC resulted in improved smooth muscle content in the bladder tissue, significantly increased β-III tubulin expression of the PN, and enhanced SDF-1 expression (P<0.05). The bladder wall repair can be attributed to the overexpression of SDF-1 by SDF-1 eMSCs. Significantly increased SDF-1 expression was obtained in the Injury+SDF-1 eMSC group (P<0.05). The crushed PN also showed significant recovery in the Injury+SDF-1 eMSC group (P<0.05). In conclusion, our results indicate that SDF-1 eMSCs express more SDF-1 in vivo, thereby facilitating the repair of injured nerve and recovery of NB in rats.