Evaluation of Misoprostol Cytoprotection of the Bladder with Cyclophosphamide (Cytoxan) Therapy

Gray, Katie; Engelmann, U.; Johnson, Ernest H.; Fishman, Irving J.

doi:10.1016/s0022-5347(17)44929-9

Cited by 121 publications

(84 citation statements)

References 16 publications

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“…This improvement is thought to result from a decrease in NO production. In addition, CP produced a decrease in the endogenous antioxidant compound GSH and an elevation of lipid peroxidation in urinary bladder [16,[18][19][20][21][22]. Our findings are in agreement with those of these studies, in which there was a significant depletion of GSH pool and a significant increase in lipid peroxides Fig.…”

Section: Discussionsupporting

confidence: 91%

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Protective Effect of Seleno-l-Methionine on Cyclophosphamide-Induced Urinary Bladder Toxicity in Rats

Ayhancı

Yaman

Şahıntürk

et al. 2009

Biol Trace Elem Res

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Cyclophosphamide (CP) is a widely used antineoplastic drug, which could cause toxicity of the normal cells due to its toxic metabolites. Its urotoxicity may cause doselimiting side effects like hemorrhagic cystitis. Overproduction of reactive oxygen species (ROS) during inflammation is one of the reasons of the urothelial injury. Selenoproteins play crucial roles in regulating ROS and redox status in nearly all tissues; therefore, in this study, the urotoxicity of CP and the possible protective effects of seleno-L-methionine (SLM) on urinary bladder of rats were investigated. Intraperitoneal (i.p.) administration of 50, 100, or 150 mg/kg CP induced cystitis, in a dose-dependent manner, as manifested by marked congestion, edema and extravasation in rat urinary bladder, a marked desquamative damage to the urothelium, severe inflammation in the lamina propria, focal erosions, and polymorphonuclear (PMN) leukocytes associated with occasional lymphocyte infiltration determined by macroscopic and histopathological examination. In rat urinary bladder tissue, a significant decrease in the endogenous antioxidant compound glutathione, and elevation of lipid peroxidation were also noted. Pretreatment with SLM (0.5 or 1 mg/kg) produced a significant decrease in the bladder edema and caused a marked decrease in vascular congestion and hemorrhage and a profound improvement in the histological structure. Moreover, SLM pretreatment decreased lipid peroxide significantly in urinary bladder Biol Trace Elem Res (2010) 134:98-108

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Section: Discussionsupporting

confidence: 91%

“…The main features of HC are urothelial damage, transmural edema, hemorrhage, mucosal ulceration, and epithelial necrosis. These can be demonstrated within 24 h of a single dose [18]. The urotoxicity of CP is thought to be due to the formation of acrolein that damages the urothelium [19,20].…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Seleno-l-Methionine on Cyclophosphamide-Induced Urinary Bladder Toxicity in Rats

Ayhancı

Yaman

Şahıntürk

et al. 2009

Biol Trace Elem Res

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“…Bladders were examined macroscopically for edema and hemorrhage according to pre-established criteria 13 . Edema was considered severe (3+) when fluid was seen externally and internally in the bladder wall; moderate (2+) when confined to the mucosa; mild (1+) between normal and moderate, and none (0) as normal.…”

Section: Macroscopic Examination Of Bladdermentioning

confidence: 99%

“…Histological damage was scored on a scale of (0) -normal epithelium, (1)-mild changes involving a decrease in epithelial cells, flattening with submucosal edema, mild hemorrhage and few ulcerations, and (2)-severe changes, including mucosal erosion, inflammatory cell infiltration, fibrin deposition, hemorrhage and multiple ulcerations 13 . The slides were evaluated in a blind fashion.…”

Section: Microscopy Of Bladder and Uretermentioning

confidence: 99%

Protective effect of simvastatin in the cyclophosphamide-induced hemohrragic cystitis in rats

et al. 2010

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PURPOSE: Cyclophosphamide (CYP) is an antineoplastic agent used for the treatment of many neoplastic and inflammatory diseases. Hemorrhagic cystitis is a frequent side effect of CYP. Several studies show that simvastatin has important pleiotropic (anti-inflammatory and immunomodulatory) effects. The purpose of the study was to investigate the effect of simvastatin on bladder, ureter and kidney injury caused by CYP. METHODS: Adult male Wistar rats were randomly divided into three groups. The CYP/SIM group received simvastatin microemulsion by gavage during 7 days (10 mg/kg body wt) before the administration of CYP and the CYP/SAL group rats received saline 0.9%. The control rats were not treated. After that, all rats were treated with a single dose of CYP 200 mg/kg body wt intraperitoneally. The rats were killed 24 h after CYP administration. Plasma cytokines (TNF-α, IL-1β, IL-6) were measured by ELISA. Macro and light microscopic study was performed in the bladder, kidney and ureter. RESULTS: In the bladders of CYP/SIMV treated rats edema of lamina propria with epithelial and sub-epithelial hemorrhage were lower than in CYP/SAL treated rats. The scores for macroscopic and microscopic evaluation of bladder and ureter were significantly lower in CYP/SIMV rats than in CYP/SAL rats. The kidney was not affected. The expression of TNF-α, IL-1β and IL-6 was significatly lower in CF/SINV rats (164.8±22, 44.8±8 and 52.4±13) than in CF/SAL rats (378.5±66, 122.9±26 e 123.6±18), respectively. CONCLUSION: The results of the current study suggest that simvastatin pretreatment attenuated CYP-induced urotelium inflammation and decreased the activities of cytokines.

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“…Histological examination was performed by a pathologist in a single-blind fashion. Edema, bleeding, and histological changes were evaluated according to the criteria of Gray et al (14) as follows: edema was considered severe (3+) when fluid was seen externally and internally on the walls of the bladder, moderate (2+) when confined to the internal mucosa, mild (1+) when normal to moderate, and absent (0). Hemorrhage was scored as follows: 3+, intravesical clots; 2+, mucosal hematomas; 1+, telangiectasia or dilatation of the bladder vessels; 0, normal.…”

mentioning

confidence: 99%

Pharmacological and histopathological study of cyclophosphamide-induced hemorrhagic cystitis - comparison of the effects of dexamethasone and Mesna

Morais

Belarmino-Filho

Brito

et al. 1999

Braz J Med Biol Res

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Chemotherapy with oxazaphosphorines, such as cyclophosphamide (CYP), is often limited by unacceptable urotoxicity. Without uroprotection, hemorrhagic cystitis (HC) becomes dose-limiting. To compare the uroprotective efficacy of classical 2-mercaptoethanesulfonic acid (Mesna) treatment with dexamethasone in CYP-induced HC, male Wistar rats (150-200 g; N = 6 in each group) were treated with saline or Mesna (40 mg/kg, ip) immediately and 4 and 8 h after ip administration of CYP (200 mg/kg). One, 2 or 3 doses of Mesna were replaced with dexamethasone (1 mg/kg, ip). The animals were sacrificed 24 h later. Cystitis was evaluated by determining the changes in bladder wet weight (BWW) and by macroscopic and microscopic analysis. CYP treatment induced a marked increased in BWW (162%, P<0.05), which was significantly inhibited by treatment with 3 doses of Mesna (P<0.05; 80%). The replacement of 1 or 2 doses of Mesna with dexamethasone reduced the increase in BWW by 83.3 and 95%, respectively. Macroscopic analysis of the bladder of rats with CYPinduced HC showed severe edema and hemorrhage, confirmed by microscopic analysis, that also showed mucosal erosion, inflammatory cell infiltration and ulcerations. The replacement of 1 or 2 doses of Mesna with dexamethasone inhibited the CYP-induced increase in BWW and almost abolished the macroscopic and microscopic alterations, with no significant difference between the effects of Mesna and dexamethasone, indicating that both drugs were efficient in blocking HC. However, although the replacement of all Mesna doses with dexamethasone reduced the edema, it did not prevent HC, suggesting that Mesna is necessary for the initial uroprotection.

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Evaluation of Misoprostol Cytoprotection of the Bladder with Cyclophosphamide (Cytoxan) Therapy

Cited by 121 publications

References 16 publications

Protective Effect of Seleno-l-Methionine on Cyclophosphamide-Induced Urinary Bladder Toxicity in Rats

Protective Effect of Seleno-l-Methionine on Cyclophosphamide-Induced Urinary Bladder Toxicity in Rats

Protective effect of simvastatin in the cyclophosphamide-induced hemohrragic cystitis in rats

Pharmacological and histopathological study of cyclophosphamide-induced hemorrhagic cystitis - comparison of the effects of dexamethasone and Mesna

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