Protective effects of l-glutamine on the bladder wall of rats submitted to pelvic radiation

Barcellos, Leilane M; Costa, Waldemar S.; Medeiros, Jorge L.; Rocha, Beatriz; Sampaio, Francisco J.B.; Cardoso, Luiz E.M.

doi:10.1016/j.micron.2013.01.001

Cited by 8 publications

(10 citation statements)

References 37 publications

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“…In this irradiation methodology, other organs located close to the colon, like the bladder, the prostate or seminal vesicles may be in the irradiated field. Irradiation of these organs might induce time-dependent tissue damage such as what has already been described for the bladder [19][20][21]. Physiological cross-talk between different visceral organs is necessary to function in a coordinated manner [22].…”

Section: Discussionmentioning

confidence: 89%

Mesenchymal Stem Cell Therapy Stimulates Endogenous Host Progenitor Cells to Improve Colonic Epithelial Regeneration

Sémont¹,

Demarquay²,

Bessout³

et al. 2013

PLoS ONE

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Patients who undergo pelvic radiotherapy may develop severe and chronic complications resulting from gastrointestinal alterations. The lack of curative treatment highlights the importance of novel and effective therapeutic strategies. We thus tested the therapeutic benefit of mesenchymal stem cells (MSC) treatment and proposed molecular mechanisms of action. MSC efficacy was tested in an experimental model of radiation-induced severe colonic ulceration histologically similar to that observed in patients. In this model, MSC from bone marrow were administered intravenously, immediately or three weeks (established lesions) after irradiation. MSC therapy reduces radiation-induced colonic ulceration and increases animal survival. MSC treatment induces therapeutic efficacy whatever the time of cell infusion. Infused-MSC engraft in the colon but also increase endogenous MSC mobilization in blood that have lasting benefits over time. In vitro analysis demonstrates that the MSC effect is mediated by paracrine mechanisms through the non-canonical WNT (Wingless integration site) pathway. In irradiated rat colons, MSC treatment increases the expression of the non-canonical WNT4 ligand by epithelial cells. The epithelial regenerative process is improved after MSC injection by stimulation of colonic epithelial cells positive for SOX9 (SRY-box containing gene 9) progenitor/stem cell markers. This study demonstrates that MSC treatment induces stimulation of endogenous host progenitor cells to improve the regenerative process and constitutes an initial approach to arguing in favor of the use of MSC to limit/reduce colorectal damage induced by radiation.

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Section: Discussionmentioning

confidence: 89%

Mesenchymal Stem Cell Therapy Stimulates Endogenous Host Progenitor Cells to Improve Colonic Epithelial Regeneration

Sémont¹,

Demarquay²,

Bessout³

et al. 2013

PLoS ONE

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“…8 The radiation dose calls as intermediate dose, between low doses typically in the range of 0.015–2 Gy and high doses in the range of 30–45 Gy. 2…”

Section: Discussionmentioning

confidence: 99%

“…8 The radiation dose calls as intermediate dose, between low doses typically in the range of 0.015-2 Gy and high doses in the range of 30-45 Gy. 2 Although radiotherapy is widely used in the treatment of cancer, the response of tissues to radiation is variable. 9 It was reported that irradiation of the urinary bladder results in morphological changes, such as mucosal edema and hyperemia.…”

Section: Discussionmentioning

confidence: 99%

“…Barcellos et al reported that radiation-induced modifications in the bladder wall are time-dependent. 2…”

Section: Introductionmentioning

confidence: 99%

“…Barcellos et al reported that radiation-induced modifications in the bladder wall are time-dependent. 2 The urinary bladder collects urine and functions as a temporary reservoir for urine. The bladder is covered by urothelium that consists of three to seven layers of transitional cells.…”

Section: Introductionmentioning

confidence: 99%

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POMC expression of the urothelium of the urinary bladder of mice submitted to pelvic radiation

et al. 2016

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Objective: Patients who have had pelvic radiotherapy as part of their cancer therapy may develop subsequent urinary bladder injury. The acute changes that the urothelium undergo after radiation are known, but the healing mechanism of the urothelium of the urinary bladder after pelvic radiotherapy is not clearly understood. Proopiomelanocortin (POMC) peptides, which have immunomodulatory effects, are produced locally in sites outside of the central nervous system. This study aims to determine the role of POMC expression in the urothelium during radiation injury. Methods: Twenty-four male Swiss Albino mice were divided into four groups. A single-fractioned 10 Gy of ionizing radiation was applied to the pelvic zone of all mice with Cobalt-60 radiotherapy. The first group 1, which consisted intact animal and not irradiated was the control group, and the second, third, and fourth groups were euthanized after 24 h (Group 2), 48 h (Group 3), and 7 days (Group 4) after irradiation. All bladders were prepared for histochemical analysis using hematoxylin eosin (H&E) and immunohistochemical analysis using anti-POMC antibody. Results: No morphological differences were seen in all the group samples stained with H&E. POMC expression of the urothelium of bladder tissue samples shows different staining levels. Group 1 (96.7 ± 7.68), Group 2 (88.3 ± 8.04), and Group 3 (85.10 ± 10.9) were very weakly stained, but the POMC immunoreactivity of Group 4 (113.0 ± 12.8) was observed to be strong. Conclusion: Expression of POMC from urothelium seems to prevent bladder damage from radiation supplying differentiation and restoration of the urothelium.

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Impact of prostatic radiation therapy on bladder contractility and innervation

Turner

Powers

Odom

et al. 2021

Neurourology and Urodynamics

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Aims: To determine the effect of prostatic radiation therapy (RT) on bladder contractility and morphology, and axon, or neuron profiles within the detrusor and major pelvic ganglia (MPG) in male rats. Methods: Male Sprague-Dawley rats (8 weeks) received a single dose of prostatic RT (0 or 22 Gy). Bladders and MPG were collected 2-and 10-weeks post-RT. Detrusor contractile responses to carbachol and electrical field stimulation (EFS) were measured. Bladders were stained with Masson's trichrome, and antibodies for nonspecific neuronal marker, cholinergic nerve marker choline acetyltransferase (ChAT), and alpha-smooth muscle actin.MPG gene expression was assessed by quantitative polymerase chain reaction for ubiquitin carboxy-terminal hydrolase L1 (Uchl1) and Chat. Results: At 2 weeks post-RT, bladder smooth muscle, detrusor cholinergic axon profiles, and MPG Chat gene expression were increased (p < .05), while carbachol and EFS-mediated contractions were decreased (p < .05). In contrast, at 10 weeks post-RT, nerve-mediated contractions were increased compared with control (p < .05), while bladder smooth muscle, detrusor cholinergic axon profiles, MPG Chat expression, and carbachol contractions had normalized. At both 2-and 10-weeks post-RT, there was no change in detrusor nonspecific axon profiles and MPG Uchl1 expression. Conclusion:In a rat model, RT of the prostate and MPG was associated with early changes in MPG Chat gene expression, and bladder cholinergic axon profiles and smooth muscle content which resolved over time. After RT recovery, bladder contractility decreased early and increased by 10 weeks. Longterm changes to the MPG and increased bladder cholinergic axons may contribute to RT-induced bladder dysfunction in prostate cancer survivors.

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Protective effects of l-glutamine on the bladder wall of rats submitted to pelvic radiation

Cited by 8 publications

References 37 publications

Mesenchymal Stem Cell Therapy Stimulates Endogenous Host Progenitor Cells to Improve Colonic Epithelial Regeneration

Mesenchymal Stem Cell Therapy Stimulates Endogenous Host Progenitor Cells to Improve Colonic Epithelial Regeneration

POMC expression of the urothelium of the urinary bladder of mice submitted to pelvic radiation

Impact of prostatic radiation therapy on bladder contractility and innervation

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