Histological changes in bladders of patients submitted to ifosfamide chemotherapy even with mesna prophylaxis

Lima, Marcos Venício Alves; Ferreira, Francisco Valdeci; Macedo, Francisco; Brito, Gerly Anne de Castro; Ribeiro, Ronaldo A.

doi:10.1007/s00280-006-0307-5

Cited by 34 publications

(25 citation statements)

References 18 publications

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“…On the other hand, etoricoxib did not exhibit this side eVect even with higher dose. It was shown that signiWcative degrees of bladder damage in patients submitted to ifosfamide-based chemotherapy even with the classical prevention with three doses of mesna and that dexamethasone added to mesna was more eYcient in preventing IFS-induced HC when mesna was used alone in rats (Vieira et al 2003;Lima et al 2007). This was similar with our results where we added COX-2 inhibitors to mesna.…”

Section: Experimental Groups Urothelial Cells Sub-epithelial Cells Pasupporting

confidence: 93%

“…However, despite positive results after the prophylactic use of mesna for preventing HC, bladder protection is not always achieved, particularly when a lesion has already been established (Shulman 1993). The occurrence of cystitis despite Mesna was observed either experimentally (Vieira et al 2003) or clinically (Lima et al 2007). These facts enhance the importance of studies that investigate the mechanisms involved in bladder lesions resulting from alkylating agent therapies.…”

Section: Introductionmentioning

confidence: 78%

“…Mesna has been used for more than a decade to reduce the incidence of HC, but it does not always provide uroprotection either experimentally and clinically (Vieira et al 2003;Lima et al 2007). Mesna seems to be necessary for the initial uroprotection through its neutralizing eVect of acrolein, while COX-inhibitors may inhibit PGs production that follow focusing on COX-2 expression.…”

Section: Experimental Groups Urothelial Cells Sub-epithelial Cells Pamentioning

confidence: 96%

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Cyclooxygenase-2 expression on ifosfamide-induced hemorrhagic cystitis in rats

Macedo

Baltazar

Almeida

et al. 2007

J Cancer Res Clin Oncol

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Section: Experimental Groups Urothelial Cells Sub-epithelial Cells Pasupporting

confidence: 93%

Section: Introductionmentioning

confidence: 78%

Section: Experimental Groups Urothelial Cells Sub-epithelial Cells Pamentioning

confidence: 96%

See 1 more Smart Citation

Cyclooxygenase-2 expression on ifosfamide-induced hemorrhagic cystitis in rats

Macedo

Baltazar

Almeida

et al. 2007

J Cancer Res Clin Oncol

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“…However, despite positive results after the prophylactic use of mesna for preventing HC, bladder protection is not always achieved, particularly when a lesion has already been established [6]. The occurrence of cystitis despite mesna was observed both experimentally [7] and clinically [8]. These facts enhance the importance of studies that investigate the mechanisms involved in bladder lesions resulting from alkylating agent therapies.…”

Section: Introductionmentioning

confidence: 65%

Interleukin-4 Modulates the Inflammatory Response in Ifosfamide-Induced Hemorrhagic Cystitis

et al. 2011

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We investigated whether interleukin-4 (IL-4) is present and capable of reducing inflammatory changes seen in ifosfamide-induced hemorrhagic cystitis. Male Swiss mice were treated with saline or ifosfamide alone or ifosfamide with the classical protocol with mesna and analyzed by changes in bladder wet weight (BWW), macroscopic and microscopic parameters, exudate, and hemoglobin quantification. In other groups, IL-4 was administered intraperitoneally 1 h before ifosfamide. In other experimental groups, C57BL/6 WT (wild type) and C57BL/6 WT IL-4 (-/-) knockout animals were treated with ifosfamide and analyzed for changes in BWW. Quantification of bladder IL-4 protein by ELISA in control, ifosfamide-, and mesna-treated groups was performed. Immunohistochemistry to tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) as well as protein identification by Western blot assay for inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was carried out on ifosfamide- and IL-4-treated animals. In other experimental groups, antiserum against IL-4 was given 30 min before ifosfamide. In IL-4-treated animals, the severity of hemorrhagic cystitis was significantly milder than in animals treated with ifosfamide only, an effect that was reverted with serum anti-IL-4. Moreover, knockout animals for IL-4 (-/-) exhibit a worse degree of inflammation when compared to C57BL/6 wild type. Exogenous IL-4 also attenuated TNF-α, IL-1β, iNOS, and COX-2 expressions in ifosfamide-treated bladders. IL-4, an anti-inflammatory cytokine, attenuates the inflammation seen in ifosfamide-induced hemorrhagic cystitis.

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“…[29][30][31] Mucosal lesions, such as edema or hemorrhage, will occur and mucosal permeability will increase after CYP treatment. 32 It is suspected that nitric oxide release, 33 inflammation and hyperactivity 34 after CYP treatment is associated with the disruption of mucosa. Bladder HA instillation helps prevent mucosa from pathological damages.…”

Section: Discussionmentioning

confidence: 99%

Effect of hyaluronic acid on urine nerve growth factor in cyclophosphamide‐induced cystitis

Cheng

Lin

et al. 2011

Int J of Urology

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Objectives: To investigate how hyaluronic acid (HA) affects nerve growth factor (NGF) production and bladder overactivity in a cyclophosphamide (CYP)-induced cystitis rat model. Methods: Female Sprague-Dawley rats received three intermittent intraperitoneal injections of CYP (75 mg/kg) or saline. Before or after CYP injection, HA was given intravesically and urine NGF was checked with creatinine correction. Bladder function was evaluated by cystometrograms under Zoletil anesthesia. Furthermore, the effect of HA was counteracted with hyaluronidase (HYAL). Bladder structural change was compared among groups with trichrome stain. Results: The intercontraction interval (ICI) significantly decreased in CYP-injected rats in comparison to the salineinjected controls. In the CYP-injected groups, bladder HA instillation significantly increased the ICI, but did not change the maximum voiding pressure in comparison to the saline instillation. NGF production significantly increased in CYP-injected rats, but decreased significantly with HA treatment. Treatment with HA had a more significant effect on urine NGF and the use of HYAL would eliminate this effect. Specific staining showed mucosa swelling after CYP treatment. Little HA coating on bladder mucosa could be found in HA-treated rats. Conclusions: Present findings raise the possibility that HA could be an effective treatment for CYP-related bladder overactivity through the involvement of NGF signaling.

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Histological changes in bladders of patients submitted to ifosfamide chemotherapy even with mesna prophylaxis

Cited by 34 publications

References 18 publications

Cyclooxygenase-2 expression on ifosfamide-induced hemorrhagic cystitis in rats

Cyclooxygenase-2 expression on ifosfamide-induced hemorrhagic cystitis in rats

Interleukin-4 Modulates the Inflammatory Response in Ifosfamide-Induced Hemorrhagic Cystitis

Effect of hyaluronic acid on urine nerve growth factor in cyclophosphamide‐induced cystitis

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