Interleukin-11 attenuates ifosfamide-induced hemorrhagic cystitis

Mota, José Maurício; Brito, Gerly A. C.; Loiola, Raphael T.; Cunha, Fernando de Queiróz; Ribeiro, Ronaldo de Albuquerque

doi:10.1590/s1677-55382007000500013

Cited by 10 publications

(6 citation statements)

References 18 publications

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“…Moreover, COX-2 expression seems to be regulated by TNF-α and IL-1β since blockade with TNF-α and IL-1β inhibitors decreased significantly COX-2 expression [11]. Recently, it has been shown that interleukin-11 partially prevents ifosfamide-induced experimental hemorrhagic cystitis [22] by possibly inhibiting TNF-α, IL-1β, and nitric oxide release [23]. Another study showed that IL-4 is present after cyclosphophamide-induced hemorrhagic cystitis either acutely or chronically [17]; however, it did not address the antiinflammatory mechanisms of IL-4.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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“…The rats were given an intraperitoneal injection of CYP along with intravenous infusion of Evans blue dye (25 mg/kg), 30 min before execution. 17 After execution, the bladders were excised, dissected, and cultured for dye extraction in incubator at 56 °C for 6 h (overnight) in vials containing formamide solution (1 mL/bladder). By measuring the absorbance at 600 nm and comparing it to the standard curve of Evans blue dye μg/bladder, the concentration of extracted dye was determined.…”

Section: Methodsmentioning

confidence: 99%

“…The rats were given an intraperitoneal injection of CYP along with intravenous infusion of Evans blue dye (25 mg/kg), 30 min before execution . After execution, the bladders were excised, dissected, and cultured for dye extraction in incubator at 56 °C for 6 h (overnight) in vials containing formamide solution (1 mL/bladder).…”

Section: Methodsmentioning

confidence: 99%

Boswellic Acids, Pentacyclic Triterpenes, Attenuate Oxidative Stress, and Bladder Tissue Damage in Cyclophosphamide-Induced Cystitis

et al. 2022

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Boswellic acids, derived from the Boswellia serrata plant, have been demonstrated to have anti-inflammatory properties in experimental animal models. The present study was aimed to evaluate the uro-protective effect of boswellic acids in rats with cyclophosphamide-induced cystitis. Interstitial cystitis was induced by cyclophosphamide (CYP). In order to analyze the reduction of the urothelial damage, the bladder weight, the nociception response, and the Evans blue dye extravasation from the bladder were evaluated. To investigate the involvement of lipid peroxidation and enzymatic antioxidants CAT, SOD, and GPX and MPO and NO were evaluated. IL-6 and TNF-α were measured by the ELISA immunoassay technique. The results showed that pretreatment with boswellic acids significantly reduced urothelial damage which was accompanied by a decrease in the activity of MDA, CPO, and NO levels and prevention of the depletion of CAT, SOD, and GPX. The levels of IL-6 and TNF-α were dramatically reduced by boswellic acids. Histopathological findings revealed a considerable reduction in cellular infiltration, edema, epithelial denudation, and bleeding. Our findings showed that boswellic acids, by their antioxidant and anti-inflammatory properties, negate the detrimental effects of cyclophosphamide on the bladder, suggesting boswellic acids as promising therapeutic alternatives for cystitis.

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“…The incidence of HC after the administration of oxazaphosphorine alkylating agents without mesna prophylaxis was reported to be as high as 68%, on the other hand, even with mesna prophylaxis, the incidence of HC can reach between 5% and 30%. [234] Thus, new approaches are being investigated to understand the pathogenesis of HC and to determine its risk factors and steps for its prevention. [35]…”

Section: Introductionmentioning

confidence: 99%

Protective effect of ketamine against hemorrhagic cystitis in rats receiving ifosfamide

et al. 2014

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Objective:To investigate the possible protective effect of a single dose of ketamine and the synergistic effect between ketamine and 2-mercaptoethane sulfonate (mesna) against ifosfamide-induced hemorrhagic cystitis.Materials and Methods:35 adult female wistar rats were divided into five groups and pretreated with ketamine at 10 mg/kg and/or mesna 400 mg/kg 30 minutes before intraperitoneal injection of IFS (400 mg/kg) or with saline (control group). Hemorrhagic cystitis was evaluated 24 hours after IFS injection according to bladder wet weight (BWW), and microscopic changes, i.e. edema, hemorrhage, cellular infiltration, and urothelial desquamation. The markers of oxidative damage including nitric oxide (NO) and malondialdehyde (MDA) levels and the expressions of tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL-1β), inducible nitric oxide synthase (i-NOS) and endothelial nitric oxide synthase (e-NOS) were also assayed in the bladder tissues.Results:Pretreatment with ketamine alone or ketamine in combination with mesna reduced the IFS-induced increase of BWW (58,47% and 63,33%, respectively, P < 0.05). IFS- induced microscopic alterations were also prevented by ketamine with or without mesna (P < 0.05). In addition, also statistically insignificant, the bladder tissue expressions of IL-1β were lower in ketamine and/or mesna-receiving groups (P > 0,05). The parameters of oxidative stress, the NO and the MDA contents of the bladder tissues of the study groups were not different.Conclusion:The results of the present study suggest that a single dose of ketamine pretreatment attenuates experimental IFS-induced bladder damage. It is therefore necessary to investigate ketamine locally and systematically with various dosing schedulesin order to reduce the bladder damage secondary to oxazaphosphorine-alkylating agents and these results may widen the spectrum of ketamine.

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Interleukin-11 attenuates ifosfamide-induced hemorrhagic cystitis

Abstract: Our results demonstrate a protective effect of rhIL-11 on experimental IFS- induced HC, not previously reported.

Cited by 10 publications

References 18 publications

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

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

Boswellic Acids, Pentacyclic Triterpenes, Attenuate Oxidative Stress, and Bladder Tissue Damage in Cyclophosphamide-Induced Cystitis

Protective effect of ketamine against hemorrhagic cystitis in rats receiving ifosfamide

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