Hypoactivity of rat detrusor muscle in a model of cystitis: exacerbation by non-selective COX inhibitors and amelioration by a selective DP1 receptor antagonist

Bassiouni, Wesam; Daabees, Tahia T.; Norel, Xavier; Senbel, Amira

doi:10.1007/s00210-018-01599-7

Cited by 4 publications

(3 citation statements)

References 50 publications

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“…Ach and ATP are the main neurotransmitters that contract the detrusor muscle. The receptors for Ach (M2 and M3) and ATP(P2X1) present in the detrusor smooth muscle (25). The release of Ach from cholinergic fibers and its binding with muscarinic receptors constitute the major mechanism of detrusor contraction (26).…”

Section: Author Contributionsmentioning

confidence: 99%

Ovarektomize Dişi Sıçanlarda 1,1-Dimetilbiguanit Hidroklorid (Metformin)'in Detrüsör Kas Kontraktil Yanıtı Üzerine Etkileri

TURAN

Erdem

ERGENÇ

et al. 2022

Türk Diyab Obez / Turk J Diab Obes

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Aim: Menopause is defined as the depletion of the ovarian follicular reserve followed by the cessation of menstrual cycles. It has been reported that gonadal steroid hormones play an important role in bladder function in women. Changes in urine pattern including overactive bladder, stress incontinence and recurrent urinary tract infections occur as a result of menopause. 1,1-dimethylbiguanide hydrochloride, metformin, (MET) is an oral anti-diabetic drug used to reduce hepatic glucose production and peripheral insulin resistance. Recent studies have revealed that MET has a protective effects in diabetes induced bladder dysfunction. The aim of this study was to test the therapeutic potential of MET in detrusor contractile function of ovariectomized (OVX) female rats. Material and Methods: Bilateral ovariectomy was performed to eliminate endogenous gonadal steroids secretion. Four groups are designed with 8 animals in each group: Control, MET-administered control, OVX, and MET-administered OVX groups. MET (25 mg/ kg) was administered daily by oral gavage for 14 days. Contractile activity of isolated bladder muscle strips were evaluated in vitro organ bath. The contractile responses of detrusor strips were determined using different doses of carbachol (10-8-10-2M) and purinergic agonist ATP. The relaxation response of strips were determined by isoproterenol Results: The contractile responses of detrusor muscle strips to carbachol at doses 10-5-10-2 M were decreased in the OVX group compared to control and MET treated control groups. MET treatment partially reversed the reduction in OVX-induced contractile responses at 10-2 and 10 -3 M carbachol doses. There were no statistically significant difference in relaxation response between the experimental groups. Conclusion: Our findings suggest that treatment with MET could be the new potential therapeutic agent against bladder dyfunction in postmenopausal women. Further studies are needed for the therapeutic potential of MET in detrusor dysfunction induced by menopause.

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Section: Author Contributionsmentioning

confidence: 99%

Ovarektomize Dişi Sıçanlarda 1,1-Dimetilbiguanit Hidroklorid (Metformin)'in Detrüsör Kas Kontraktil Yanıtı Üzerine Etkileri

TURAN

Erdem

ERGENÇ

et al. 2022

Türk Diyab Obez / Turk J Diab Obes

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“…In bladder tissues, prostanoids are produced abundantly to maintain bladder homeostasis; the primary prostanoids synthesized in the human bladder are PGI 2 , followed by PGE 2 , PGF 2α and TXA 2 18 . Various studies have shown that prostanoids alter the bladder motor activity and micturition reflex, 19,20 and prostanoids have also been suggested to be involved in bladder inflammation. The amount of both PGI 2 and PGE 2 in bladder tissues and PGE 2 in urine increase with hemorrhagic cystitis 21,22 .…”

Section: Introductionmentioning

confidence: 99%

Absence of prostacyclin greatly relieves cyclophosphamide‐induced cystitis and bladder pain in mice

et al. 2021

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Cyclophosphamide (CP) has been widely used in the treatment of various malignancies and autoimmune diseases, but acrolein, a byproduct of CP, causes severe hemorrhagic cystitis as the major side effect of CP. On the other hand, a large amount of prostacyclin (PGI 2 ) is produced in bladder tissues, and PGI 2 has been shown to play a critical role in bladder homeostasis. PGI 2 is biosynthesized from prostaglandin (PG) H 2 , the common precursor of PGs, by PGI 2 synthase (PTGIS) and is known to also be involved in inflammatory responses. However, little is known about the roles of PTGIS-derived PGI 2 in bladder inflammation including CP-induced hemorrhagic cystitis. Using both genetic and pharmacological approaches, we here revealed that PTGIS-derived PGI 2 -IP (PGI 2 receptor) signaling exacerbated CP-induced bladder inflammatory reactions. Ptgis deficiency attenuated CP-induced vascular permeability and chemokine-mediated neutrophil migration into bladder tissues and then suppressed hemorrhagic cystitis. Treatment with RO1138452, an IP selective antagonist, also suppressed CP-induced cystitis. We further found that cystitis-related nociceptive behavior was also relieved in both Ptgis −/− mice and RO1138452-treated mice. Our findings may provide new drug targets for bladder inflammation and inflammatory pain in CP-induced hemorrhagic cystitis.

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“…It is Estrogen-positive (ER-positive) and progesterone receptor (PR)-positive [19]. MCF-7 is a poorly-hostile and non-protruding cell line [18], normally being considered to have low metastatic potential [19,20]. Despite certain advances in cancer therapy, still there is considerable demand for developing efficient therapeutic agents.…”

Section: Introductionmentioning

confidence: 99%

Crystal Structure, Hirshfeld Surfaces and Energy Framework Studies of a Biologically Active Compound (3E)-3- (2,4- dimethoxybenzyldene) -2,3-dihydro- 4H-chromen-4-one

Hemalatha

Jonathan

Shirmila

et al. 2021

CSIJ

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A new chalcone derivative (3E)-3-(2,4-dimethoxybenzyldene)-2,3-dihydro-4H-chromen-4-one (DBDB) has been synthesized by following the Claisen-Schmidt condensation reaction method at ambient temperature using the slow evaporation technique. The 3D crystal structure was solved using the single-crystal X-ray diffraction method (XRD). XRD intensity data reveal that the title compound crystallizes in an orthorhombic crystal system with non-centrosymmetric space group P21 21 21. The crystallographic parameters such as bond lengths, bond angles, torsion angles were estimated and are found to be in the normal range and comparable with the literature values. The unit cell packing of the molecules shows that the adjacent molecules are linked via C-H…O hydrogen bonds. Hirshfeld surfaces namely dnorm, electrostatic potential, shape index, and curvedness were analyzed to visualize and to evaluate the weak intermolecular interactions, positive and negative potential regions, C-H…π, and π…π stacking interactions, respectively. The 2D fingerprint plots for the whole and delineated interactions were generated and analyzed to estimate their contributions to the total Hirshfeld surfaces. The pairwise intermolecular interactions were calculated as the sum of four scaled energy components namely electrostatic (Eele), polarization (Epol), dispersion (Edis), and exchange-repulsion (Erep) and graphically represented as energy frameworks. The energy frameworks analysis reveals that the total stabilizing energy is highly influenced by dispersion (Edis) energy than the other components. In-vitro and in-silico investigations have also been performed for the title molecule which discloses the efficacious for use as a drug in inhibiting breast cancer cells without affecting the normal cells.

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Hypoactivity of rat detrusor muscle in a model of cystitis: exacerbation by non-selective COX inhibitors and amelioration by a selective DP1 receptor antagonist

Cited by 4 publications

References 50 publications

Ovarektomize Dişi Sıçanlarda 1,1-Dimetilbiguanit Hidroklorid (Metformin)'in Detrüsör Kas Kontraktil Yanıtı Üzerine Etkileri

Ovarektomize Dişi Sıçanlarda 1,1-Dimetilbiguanit Hidroklorid (Metformin)'in Detrüsör Kas Kontraktil Yanıtı Üzerine Etkileri

Absence of prostacyclin greatly relieves cyclophosphamide‐induced cystitis and bladder pain in mice

Crystal Structure, Hirshfeld Surfaces and Energy Framework Studies of a Biologically Active Compound (3E)-3- (2,4- dimethoxybenzyldene) -2,3-dihydro- 4H-chromen-4-one

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