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Invited Review Open Access


Chemotherapy-induced hemorrhagic cystitis: pathogenesis, pharmacological approaches and new insights

Ronaldo A. Ribeiro, Roberto C.P. Lima-Junior, Caio Abner V.G. Leite, Jose Mauricio S.C. Mota, Francisco Y.B. Macedo, Marcos V.A. Lima, Gerly A.C. Brito.

Cited by (12)

Abstract
Chemotherapy-induced hemorrhagic cystitis (HC) remains a common and life-threatening clinical complication, mainly due to the increasing usage of alkylating agents during conditioning regimen for hematopoietic cell transplantation.
Currently, mesna and hyperhydration are the two more employed preventive measures. However, these prophylactic approaches have been proven not to be completely effective, since cystoscopic and histopathologic bladder damage are evidenced. Therefore, understanding the pathogenesis of HC must be the cornerstone for the development of novel therapeutic strategies.
The purpose of this review is to examine the current knowledge regarding the pathogenesis of HC, describing the importance of transcription factors (nuclear factor kappaB), cytokines (tumor necrosis factor-╬▒, interleukin-1╬▓, -4, -6, and -8), enzymes (inducible nitric oxide synthase and cyclooxygenase-2), among other mediators, for the bladder injury. We also discuss the currently available animal models and future perspectives on the management of HC.

Key words: Cancer; Chemotherapy; Hemorrhagic cystitis; Pathogenesis


 
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REFERENCES
1.Moy B. Cystitis in patients with cancer. In: UpToDate version 20.3 via http://www.uptodate.com/contents/cystitis-in-patients-with-cancer (Accessed 15 February 2012).


2.Coggins PR, Ravdin RG, Eisman SH. Clinical evaluation of a new alkylating agent: cytoxan (cyclophosphamide). Cancer 1960; 13:1254-60.
http://dx.doi.org/10.1002/1097-0142(196011/12)13:6<1254::AID-CNCR2820130614>3.0.CO;2-U


3.Stillwell TJ, Benson RC Jr. Cyclophosphamide-induced hemorrhagic cystitis: a review of 100 patients. Cancer 1988; 61:451-7.
http://dx.doi.org/10.1002/1097-0142(19880201)61:3<451::AID-CNCR2820610308>3.0.CO;2-G


4.Seber A, Shu XO, Defor T, Sencer S, Ramsay N. Risk factors for severe hemorrhagic cystitis following BMT. Bone Marrow Transplant 1999; 23:35-40.
http://dx.doi.org/10.1038/sj.bmt.1701523
[
Pubmed]   

5.Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, Soper DE. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011; 52:e103-20.
http://dx.doi.org/10.1093/cid/ciq257
[
Pubmed]   

6.Watson NA, Notley RG. Urological complications of cyclophosphamide. Br J Urol 1973; 45:606-9.
http://dx.doi.org/10.1111/j.1464-410X.1973.tb12230.x
[
Pubmed]   

7.Shepherd JD, Pringle LE, Barnett MJ, Klingemann HG, Reece DE, Phillips GL. Mesna versus hyperhydration for the prevention of cyclophosphamide-induced hemorrhagic cystitis in bone marrow transplantation. J Clin Oncol 1991; 9:2016-20.
[
Pubmed]   

8.Vose JM, Reed EC, Pippert GC, Anderson JR, Bierman PJ, Kessinger A, Spinolo J, Armitage JO. Mesna compared with continuous bladder irrigation as uroprotection during high-dose chemotherapy and transplantation: a randomized trial. J Clin Oncol 1993; 11:1306-10.
[
Pubmed]   

9.Meisenberg B, Lassiter M, Hussein A, Ross M, Vredenburgh JJ, Peters WP. Prevention of hemorrhagic cystitis after high-dose alkylating agent chemotherapy and autologous bone marrow support. Bone Marrow Transplant 1994; 14:287-91.
[
Pubmed]   

10.Hadjibabaie M, Alimoghaddam K, Shamshiri AR, Iravani M, Bahar B, Mousavi A, Jahani M, Khodabandeh A, Anvari Y, Gholami K, Ghavamzadeh A. Continuous bladder irrigation prevents hemorrhagic cystitis after allogeneic hematopoietic cell transplantation. Urol Oncol. 2008; 26:43-6.
http://dx.doi.org/10.1016/j.urolonc.2006.12.015
[
Pubmed]   

11.Koc S, Hagglund H, Ireton RC, Perez-Simon JA, Collins SJ, Appelbaum FR. Successful treatment of severe hemorrhagic cystitis with cystectomy following matched donor allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2000; 26:899-901.
http://dx.doi.org/10.1038/sj.bmt.1702611
[
Pubmed]   

12.El-Zimaity M, Saliba R, Chan K, Shahjahan M, Carrasco A, Khorshid O, Caldera H, Couriel D, Giralt S, Khouri I, Ippoliti C, Champlin R, de Lima M. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: donor type matters. Blood 2004; 103:4674-80.
http://dx.doi.org/10.1182/blood-2003-08-2815
[
Pubmed]   

13.Lima MV, Ferreira FV, Macedo FY, de Castro Brito GA, Ribeiro RA. Histological changes in bladders of patients submitted to ifosfamide chemotherapy even with mesna prophylaxis. Cancer Chemother Pharmacol 2007; 59:643-50.
http://dx.doi.org/10.1007/s00280-006-0307-5
[
Pubmed]   

14.Gine E, Rovira M, Real I, Burrel M, Montana J, Carreras E, Montserrat E. Successful treatment of severe hemorrhagic cystitis after hemopoietic cell transplantation by selective embolization of the vesical arteries. Bone Marrow Transplant 2003; 31:923-5.
http://dx.doi.org/10.1038/sj.bmt.1703954
[
Pubmed]   

15.Manikandan R, Kumar S, Dorairajan LN. Hemorrhagic cystitis: A challenge to the urologist. Indian J Urol 2010; 26:159-66.
http://dx.doi.org/10.4103/0970-1591.65380
[
Pubmed]    [PMC Free Fulltext]   

16.Philips FS, Sternberg SS, Cronin AP, Vidal PM. Cyclophosphamide and urinary bladder toxicity. Cancer Res 1961; 21:1577-89.
[
Pubmed]   

17.Campobasso O, Berrino F. Early effects of cyclophosphamide on mouse bladder epithelium. Pathol Microbiol (Basel) 1972; 38:144-57.


18.Tolley DA, Castro JE. Cyclophosphamide-induced cystitis of the urinary bladder of rats and its treatment. Proc R Soc Med 1975; 68:169-70.
[
Pubmed]    [PMC Free Fulltext]   

19.Gray KJ, Engelmann UH, Johnson EH, Fishman IJ. Evaluation of misoprostol cytoprotection of the bladder with cyclophosphamide (Cytoxan) therapy. J Urol 1986; 136: 497-500.
[
Pubmed]   

20.Souza-Fiho MV, Lima MV, Pompeu MM, Ballejo G, Cunha FQ, Ribeiro Rde A. Involvement of nitric oxide in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis. Am J Pathol 1997; 150:247-56.
[
Pubmed]    [PMC Free Fulltext]   

21.Zhang J, Quan T, Zhou SF. Clinical pharmacology of cyclophosphamide and ifosfamide. Current Drug Therapy 2006; 1:55-84.
http://dx.doi.org/10.2174/157488506775268515


22.Ribeiro RA, Freitas HC, Campos MC, Santos CC, Figueiredo FC, Brito GA, Cunha FQ. Tumor necrosis factor-alpha and interleukin-1beta mediate the production of nitric oxide involved in the pathogenesis of ifosfamide induced hemorrhagic cystitis in mice. J Urol 2002; 167:2229-34.
http://dx.doi.org/10.1016/S0022-5347(05)65134-8


23.Vieira MM, Brito GA, Belarmino-Filho JN, Macedo FY, Nery EA, Cunha FQ, Ribeiro RA. Use of dexamethasone with mesna for the prevention of ifosfamide-induced hemorrhagic cystitis. Int J Urol 2003; 10:595-602.
http://dx.doi.org/10.1046/j.1442-2042.2003.00709.x
[
Pubmed]   

24.Chaviano AH, Gill WB, Ruggiero KJ, Vermeulen CW. Experimental cytoxan cystitis and prevention by acetylcysteine. J Urol 1985; 134:598-600.
[
Pubmed]   

25.Batista CK, Brito GA, Souza ML, Leitao BT, Cunha FQ, Ribeiro RA. A model of hemorrhagic cystitis induced with acrolein in mice. Braz J Med Biol Res 2006; 39:1475-81.
[
Pubmed]   

26.Arnold H, Bourseaux F, Brock N. Neuartige Krebs-Chemotherapeutika aus der Gruppe der zyklischen N-Lost-Phosphamidester. Naturwissenschaften 1958; 45:64-6.
http://dx.doi.org/10.1007/BF00638623


27.deVries CR, Freiha FS. Hemorrhagic cystitis: a review. J Urol 1990; 143:1-9.
[
Pubmed]   

28.Alarcon RA, Meienhofer J. Formation of the cytotoxic aldehyde acrolein during in vitro degradation of cyclophosphamide. Nat New Biol 1971; 233:250-2.


29.Cox PJ. Cyclophosphamide cystitis--identification of acrolein as the causative agent. Biochem Pharmacol 1979; 28:2045-9.
http://dx.doi.org/10.1016/0006-2952(79)90222-3


30.Scheef W, Klein HO, Brock N, Burkert H, Gunther U, Hoefer-Janker H, Mitrenga D, Schnitker J, Voigtmann R. Controlled clinical studies with an antidote against the urotoxicity of oxazaphosphorines: preliminary results. Cancer Treat Rep 1979; 63:501-5.
[
Pubmed]   

31.Gomes TN, Santos CC, Souza-Filho MV, Cunha FQ, Ribeiro RA. Participation of TNF-alpha and IL-1 in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis. Braz J Med Biol Res 1995; 28:1103-8.
[
Pubmed]   

32.Sonis ST. Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity. Oral Oncol 1998; 34:39-43.
http://dx.doi.org/10.1016/S1368-8375(97)00053-5


33.Korkmaz A, Topal T, Oter S. Pathophysiological aspects of cyclophosphamide and ifosfamide induced hemorrhagic cystitis; implication of reactive oxygen and nitrogen species as well as PARP activation. Cell Biol Toxicol 2007; 23:303-12.
http://dx.doi.org/10.1007/s10565-006-0078-0
[
Pubmed]   

34.Kiuchi H, Takao T, Yamamoto K, Nakayama J, Miyagawa Y, Tsujimura A, Nonomura N, Okuyama A. Sesquiterpene lactone parthenolide ameliorates bladder inflammation and bladder overactivity in cyclophosphamide induced rat cystitis model by inhibiting nuclear factor-kappaB phosphorylation. J Urol 2009; 181:2339-48.
http://dx.doi.org/10.1016/j.juro.2009.01.015
[
Pubmed]   

35.Oter S, Korkmaz A, Oztas E, Yildirim I, Topal T, Bilgic H. Inducible nitric oxide synthase inhibition in cyclophosphamide induced hemorrhagic cystitis in rats. Urol Res 2004; 32:185-9.
http://dx.doi.org/10.1007/s00240-003-0398-y
[
Pubmed]   

36.Macedo FY, Baltazar F, Almeida PR, Tavora F, Ferreira FV, Schmitt FC, Brito GA, Ribeiro RA. Cyclooxygenase-2 expression on ifosfamide-induced hemorrhagic cystitis in rats. J Cancer Res Clin Oncol 2008; 134:19-27.
http://dx.doi.org/10.1007/s00432-007-0237-6
[
Pubmed]   

37.Macedo FY, Baltazar F, Mourao LC, Almeida PR, Mota JM, Schmitt FC, Ribeiro RA. Induction of COX-2 expression by acrolein in the rat model of hemorrhagic cystitis. Exp Toxicol Pathol 2008; 59:425-30.
http://dx.doi.org/10.1016/j.etp.2007.10.010
[
Pubmed]   

38.Korkmaz A, Oter S, Sadir S, Coskun O, Topal T, Ozler M, Bilgic H. Peroxynitrite may be involved in bladder damage caused by cyclophosphamide in rats. J Urol 2005; 173:1793-6.
http://dx.doi.org/10.1097/01.ju.0000154344.80669.e3
[
Pubmed]   

39.Macedo FY, Mourao LT, Palheta RC Jr, Juca DM, Lima RC Jr, Neto Jde S, Magalhaes PJ, Santos AA, Souza MH, Brito GA, Ribeiro RA. Cyclooxygenase-2 contributes to functional changes seen on experimental hemorrhagic cystitis induced by ifosfamide in rat urinary bladder. Cancer Chemother Pharmacol 2011; 67:935-43.
http://dx.doi.org/10.1007/s00280-010-1392-z
[
Pubmed]   

40.Ulich TR, Whitcomb L, Tang W, O'Conner Tressel P, Tarpley J, Yi ES, Lacey D. Keratinocyte growth factor ameliorates cyclophosphamide-induced ulcerative hemorrhagic cystitis. Cancer Res 1997; 57:472-5.
[
Pubmed]   

41.Alfieri AB, Malave A, Cubeddu LX. Nitric oxide synthases and cyclophosphamide-induced cystitis in rats. Naunyn Schmiedebergs Arch Pharmacol 2001; 363:353-7.
http://dx.doi.org/10.1007/s002100000371
[
Pubmed]   

42.Malley SE, Vizzard MA. Changes in urinary bladder cytokine mRNA and protein after cyclophosphamide-induced cystitis. Physiol Genomics 2002; 9:5-13.
http://dx.doi.org/10.?1152/?physiolgenomics.?00117.?2001 [
Pubmed]   

43.Macedo FY, Mourao LT, Freitas HC, Lima-Junior RC, Wong DV, Oria RB, Vale ML, Brito GA, Cunha FQ, Ribeiro RA. Interleukin-4 modulates the inflammatory response in ifosfamide-induced hemorrhagic cystitis. Inflammation 2011.
http://dx.doi.org/10.1007/s10753-011-9319-3
[
Pubmed]   

44.Hahn NM. Learning to control cyclophosphamide induced cystitis. J Urol 2009; 181:1987-8.
http://dx.doi.org/10.1016/j.juro.2009.02.046
[
Pubmed]   

45.Baldwin AS Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 1996; 14:649-83.
http://dx.doi.org/10.1146/annurev.immunol.14.1.649
[
Pubmed]   

46.Pfeffer LM. The role of nuclear factor κB in the interferon response. J Interferon Cytokine Res 2011; 31:553-9.
http://dx.doi.org/10.1089/jir.2011.0028


47.Hehner SP, Heinrich M, Bork PM, Vogt M, Ratter F, Lehmann V, Schulze-Osthoff K, Droge W, Schmitz ML. Sesquiterpene lactones specifically inhibit activation of NF-kappa B by preventing the degradation of I kappa B-alpha and I kappa B-beta. J Biol Chem 1998; 273:1288-97
http://dx.doi.org/10.1074/jbc.273.3.1288
[
Pubmed]   

48.Parameswaran N, Patial S. Tumor necrosis factor-α signaling in macrophages. Crit Rev Eukaryot Gene Expr 2010; 20:87-103.
[
Pubmed]    [PMC Free Fulltext]   

49.Schett G, Coates LC, Ash ZR, Finzel S, Conaghan PG. Structural damage in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: traditional views, novel insights gained from TNF blockade, and concepts for the future. Arthritis Res Ther 2011; 13(Suppl 1):S4.
http://dx.doi.org/10.1186/1478-6354-13-S1-S4
[
Pubmed]    [PMC Free Fulltext]   

50.Reinisch W, Dejaco C, Feichtenschlager T, Haas T, Kaser A, Miehsler W, Novacek G, Petritsch W, Platzer R, Tilg H, Vogelsang H, Knoflach P. Infliximab therapy for Crohn's disease - a practical guideline: actualised consensus of the working group for chronic inflammatory bowel diseases of the Austrian Society for Gastroenterology and Hepatology. Z Gastroenterol. 2011; 49:534-42.
http://dx.doi.org/10.1055/s-0029-1245930
[
Pubmed]   

51.Exley AR, Cohen J, Buurman W, Owen R, Hanson G, Lumley J, Aulakh JM, Bodmer M, Riddell A, Stephens S, Riddell A, Perry M. Monoclonal antibody to TNF in severe septic shock. Lancet 1990; 335:1275-7.
http://dx.doi.org/10.1016/0140-6736(90)91337-A


52.Wachlin G, Augstein P, Schr÷der D, Kuttler B, Kl÷ting I, Heinke P, Schmidt S. IL-1beta, IFN-gamma and TNF-alpha increase vulnerability of pancreatic beta cells to autoimmune destruction. J Autoimmun 2003; 20:303-12.
http://dx.doi.org/10.1016/S0896-8411(03)00039-8


53.Logan RM, Stringer AM, Bowen JM, Yeoh AS, Gibson RJ, Sonis ST, Keefe DM. The role of pro-inflammatory cytokines in cancer treatment-induced alimentary tract mucositis: pathobiology, animal models and cytotoxic drugs. Cancer Treat Rev 2007; 33:448-60.
http://dx.doi.org/10.1016/j.ctrv.2007.03.001
[
Pubmed]   

54.Sampaio EP, Sarno EN, Galilly R, Cohn ZA, Kaplan G. Thalidomide selectively inhibits tumor necrosis factor α production by stimulated human monocytes. J Exp Med 1991; 173:699-703
http://dx.doi.org/10.1084/jem.173.3.699
[
Pubmed]   

55.Wiens A, Venson R, Correr CJ, Otuki MF, Pontarolo R. Meta-analysis of the efficacy and safety of adalimumab, etanercept, and infliximab for the treatment of rheumatoid arthritis. Pharmacotherapy 2010; 30:339-53.
http://dx.doi.org/10.1592/phco.30.4.339
[
Pubmed]   

56.Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 2008; 117:244-79.
http://dx.doi.org/10.1016/j.pharmthera.2007.10.001


57.Mossner R, Reich K. Management of severe psoriasis with TNF antagonists. Adalimumab, etanercept and infliximab. Curr Probl Dermatol 2009; 38:107-36.
http://dx.doi.org/10.1159/000232307


58.Inman RD, Maksymowych WP; CANDLE Study Group. A double-blind, placebo-controlled trial of low dose infliximab in ankylosing spondylitis. J Rheumatol 2010; 37:1203-10.
http://dx.doi.org/10.3899/jrheum.091042
[
Pubmed]   

59.Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Ann Rev Immunol 2009; 27:519-50.
http://dx.doi.org/10.1146/annurev.immunol.021908.132612
[
Pubmed]   

60.Dinarello CA. Biologic basis for interleukin-1 in disease. Blood 1996; 87:2095-147.
[
Pubmed]   

61.Weber A, Wasiliew P, Kracht M. Interleukin-1 (IL-1) pathway. Sci Signal 2010; 3:cm1.
http://dx.doi.org/10.1126/scisignal.3105cm1
[
Pubmed]   

62.Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 2011; 117:3720-32.
http://dx.doi.org/10.1182/blood-2010-07-273417
[
Pubmed]   

63.Dinarello CA. Blocking interleukin-1β in acute and chronic autoinflammatory diseases. J Intern Med 2011; 269:16-28.
http://dx.doi.org/10.1111/j.1365-2796.2010.02313.x
[
Pubmed]    [PMC Free Fulltext]   

64.Kreth S, Ledderose C, Luchting B, Weis F, Thiel M. Immunomodulatory properties of pentoxifylline are mediated via adenosine-dependent pathways. Shock 2010; 34:10-6.
http://dx.doi.org/10.1097/SHK.0b013e3181cdc3e2
[
Pubmed]   

65.Hart PH, Vitti GF, Burgess DR, Whitty GA, Piccoli DS, Hamilton JA. Potential antiinflammatory effects of interleukin 4: suppression of human monocyte tumor necrosis factor alpha, interleukin 1, and prostaglandin E2. Proc Natl Acad Sci USA 1989; 86:3803-7.
http://dx.doi.org/10.1073/pnas.86.10.3803


66.Vannier E, Miller LC, Dinarello CA. Coordinated antiinflammatory effects of interleukin 4: interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist. Proc Natl Acad Sci USA 1992; 89:4076-80.
http://dx.doi.org/10.1073/pnas.89.9.4076


67.Seitz M, Loetscher P, Dewald B, Towbin H, Ceska M, Baggiolini M. Production of interleukin-1 receptor antagonist, inflammatory chemotactic proteins, and prostaglandin E by rheumatoid and osteoarthritic synoviocytes--regulation by IFN-gamma and IL-4. J Immunol 1994; 152:2060-5.
[
Pubmed]   

68.Heymann D, Rousselle AV. gp130 Cytokine family and bone cells. Cytokine 2000; 12:1455-68.
http://dx.doi.org/10.1006/cyto.2000.0747
[
Pubmed]   

69.Nishii H, Nomura M, Fujimoto N, Matsumoto T. Up-regulation of interleukin-6 gene expression in cyclophosphamide-induced cystitis in mice: An in situ hybridization histochemical study. Int J Urol 2006; 13:1339-43.
http://dx.doi.org/10.1111/j.1442-2042.2006.01536.x
[
Pubmed]   

70.Dantas AC, Batista-Junior FF, Macedo LF, Mendes MN, Azevedo IM, Medeiros AC. Protective effect of simvastatin in the cyclophosphamide-induced hemorrhagic cystitis in rats. Acta Cir Bras 2010; 25:43-6.
http://dx.doi.org/10.1590/S0102-86502010000100011
[
Pubmed]   

71.Girard BM, Cheppudira BP, Malley SE, Schutz KC, May V, Vizzard MA. Increased expression of interleukin-6 family members and receptors in urinary bladder with cyclophosphamide-induced bladder inflammation in female rats. Front Neurosci 2011; 5:20.
http://dx.doi.org/10.3389/fnins.2011.00020
[
Pubmed]    [PMC Free Fulltext]   

72.Zhang Y, Wang L, Zhang M, Jin M, Bai C, Wang X. Potential mechanism of interleukin-8 production from lung cancer cells: an involvement of EGF-EGFR-PI3K-Akt-Erk pathway. J Cell Physiol 2012; 227:35-43.
http://dx.doi.org/10.1002/jcp.22722
[
Pubmed]   

73.Shen Y, Wang D, Wang X. Role of CCR2 and IL-8 in acute lung injury: a new mechanism and therapeutic target. Expert Rev Respir Med 2011; 5:107-14.
http://dx.doi.org/10.1586/ers.10.80
[
Pubmed]   

74.Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011; 7:33-42.
http://dx.doi.org/10.1038/nrrheum.2010.196
[
Pubmed]   

75.Gambari R, Borgatti M, Bezzerri V, Nicolis E, Lampronti I, Dechecchi MC, Mancini I, Tamanini A, Cabrini G. Decoy oligodeoxyribonucleotides and peptide nucleic acids-DNA chimeras targeting nuclear factor kappa-B: inhibition of IL-8 gene expression in cystic fibrosis cells infected with Pseudomonas aeruginosa. Biochem Pharmacol 2010; 80:1887-94.
http://dx.doi.org/10.1016/j.bcp.2010.06.047
[
Pubmed]   

76.Bhoola KD, Figueroa CD, Worthy K. Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev 1992; 44:1-80.
[
Pubmed]   

77.Marceau F, Regoli D. Bradykinin receptor ligands: therapeutic perspectives. Nat Rev Drug Discov 2004; 3:845-52.
http://dx.doi.org/10.1038/nrd1522
[
Pubmed]   

78.Stewart JM. Bradykinin antagonists: discovery and development. Peptides 2004; 25:527-32.
http://dx.doi.org/10.1016/j.peptides.2003.10.016
[
Pubmed]   

79.Maggi CA, Santicioli P, Del Bianco E, Lecci A, Guliani S. Evidence for the involvement of bradykinin in chemically-evoked cystitis in anaesthetized rats. Naunyn Schmiedebergs Arch Pharmacol 1993; 347:432-7.
http://dx.doi.org/10.1007/BF00165395
[
Pubmed]   

80.Chopra B, Barrick SR, Meyers S, Beckel JM, Zeidel ML, Ford AP, de Groat WC, Birder LA. Expression and function of bradykinin B1 and B2 receptors in normal and inflamed rat urinary bladder urothelium. J Physiol 2005; 562:859-71.
http://dx.doi.org/10.1113/jphysiol.2004.071159
[
Pubmed]    [PMC Free Fulltext]   

81.Fincham CI, Bressan A, Paris M, Rossi C, Fattori D. Bradykinin receptor antagonists--a review of the patent literature 2005-2008. Expert Opin Ther Pat 2009; 19:919-41.
http://dx.doi.org/10.1517/13543770902994389
[
Pubmed]   

82.Jawabrah Al-Hourani B, Sharma SK, Suresh M, Wuest F. Cyclooxygenase-2 inhibitors: a literature and patent review (2009-2010). Expert Opin Ther Pat 2011; 21:1339-432.
http://dx.doi.org/10.1517/13543776.2011.593510
[
Pubmed]   

83.Dannenberg AJ, Altorki NK, Boyle JO, Dang C, Howe LR, Weksler BB, Subbaramaiah K. Cyclo-oxygenase 2: A pharmacological target for the prevention of cancer. Lancet Oncol 2001; 2:544-51.
http://dx.doi.org/10.1016/S1470-2045(01)00488-0


84.Kawabata A. Prostaglandin E2 and pain--an update. Biol Pharm Bull 2011; 34:1170-3.
http://dx.doi.org/10.1248/bpb.34.1170


85.Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE. Cyclooxygenase in biology and disease. FASEB J 1998; 12:1063-73.
[
Pubmed]   

86.Hu VY, Malley S, Dattilio A, Folsom JB, Zvara P, Vizzard MA. COX-2 and prostanoid expression in micturition pathways after cyclophosphamide-induced cystitis in the rat. Am J Physiol Regul Integr Comp Physiol 2003; 284:R574-85.
http://dx.doi.org/10.?1152/?ajpregu.?00465.?2002 [
Pubmed]   

87.Maggi CA. Prostanoids as local modulators of reflex micturition. Pharmacol Res 1992; 25:13-20.
http://dx.doi.org/10.1016/S1043-6618(05)80059-3


88.Ishizuka O, Mattiasson A, Andersson KE. Prostaglandin E2-induced bladder hyperactivity in normal, conscious rats: involvement of tachykinins? J Urol 1995; 153:2034-8.
http://dx.doi.org/10.1016/S0022-5347(01)67397-X


89.Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J 2011
http://dx.doi.org/10.1093/eurheartj/ehr304
[
Pubmed]   

90.Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 1990; 87:1620-4.
http://dx.doi.org/10.1073/pnas.87.4.1620


91.Ischiropoulos H, al-Mehdi AB. Peroxynitrite-mediated oxidative protein modifications. FEBS Lett 1995; 364:279-82.
http://dx.doi.org/10.1016/0014-5793(95)00307-U


92.Ascenzi P, di Masi A, Sciorati C, Clementi E. Peroxynitrite-An ugly biofactor? Biofactors 2010; 36:264-73.
http://dx.doi.org/10.1002/biof.103
[
Pubmed]   

93.Masumoto H, Sies H. The reaction of ebselen with peroxynitrite. Chem Res Toxicol 1996; 9:262-7.
http://dx.doi.org/10.1021/tx950115u
[
Pubmed]   

94.Muller E, Dagenais P, Alami N, Rola-Pleszczynski M. Identification and functional characterization of platelet-activating factor receptors in human leukocyte populations using polyclonal anti- peptide antibody. Proc Natl Acad Sci USA 1993; 90:5818-22.
http://dx.doi.org/10.1073/pnas.90.12.5818


95.Travers JB, Huff JC, Rola-Pleszczynski M, Gelfand EW, Morelli JG, Murphy RC. Identification of functional platelet-activating factor receptors on human keratinocytes. J Invest Dermatol 1995; 105:816-23.
http://dx.doi.org/10.1111/1523-1747.ep12326581
[
Pubmed]   

96.Honda ZI, Ishii S, Shimizu T. Platelet-activating factor receptor. J Biochem 2002; 131:773-9.
http://dx.doi.org/10.1093/oxfordjournals.jbchem.a003164
[
Pubmed]   

97.Borthakur A, Bhattacharyya S, Alrefai WA, Tobacman JK, Ramaswamy K, Dudeja PK. Platelet-activating factor-induced NF-kappaB activation and IL-8 production in intestinal epithelial cells are Bcl10-dependent. Inflamm Bowel Dis 2010; 16:593-603.
http://dx.doi.org/10.1002/ibd.21092
[
Pubmed]   

98.Lock C, Hermans G, Pedotti R, Brendolan A, Schadt E, Garren H, Langer-Gould A, Strober S, Cannella B, Allard J, Klonowski P, Austin A, Lad N, Kaminski N, Galli SJ, Oksenberg JR, Raine CS, Heller R, Steinman L. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 2002; 8:500-8.
http://dx.doi.org/10.1038/nm0502-500
[
Pubmed]   

99.Chakir J, Shannon J, Molet S, Fukakusa M, Elias J, Laviolette M, Boulet LP, Hamid Q. Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-β, IL-11, IL-17, and type I and type III collagen expression. J Allergy Clin Immunol 2003; 111:1293-8.
http://dx.doi.org/10.1067/mai.2003.1557
[
Pubmed]   

100.Rickard A, Portell C, Kell PJ, Vinson SM, McHowat J. Protease-activated receptor stimulation activates a Ca2+-independent phospholipase A2 in bladder microvascular endothelial cells. Am J Physiol Renal Physiol 2005; 288:F714-21.
http://dx.doi.org/10.1152/ajprenal.00288.2004
[
Pubmed]   

101.Geppetti P, Nassini R, Materazzi S, Benemei S. The concept of neurogenic inflammation. BJU Int 2008; 101(Suppl 3):2-6.
http://dx.doi.org/10.1111/j.1464-410X.2008.07493.x
[
Pubmed]   

102.Frode-Saleh TS, Calixto JB, Medeiros YS. Analysis of the inflammatory response induced by substance P in the mouse pleural cavity. Peptides 1999; 20:259-65.
http://dx.doi.org/10.1016/S0196-9781(98)00170-3


103.Maggi CA, Catalioto RM, Criscuoli M, Cucchi P, Giuliani S, Lecci A, Lippi A, Meini S, Patacchini R, Renzetti AR, Santicioli P, Tramontana M, Zagorodnyuk V, Giachetti A. Tachykinin receptors and intestinal motility. Can J Physiol Pharmacol 1997; 75:696-703.
http://dx.doi.org/10.1139/y97-067
[
Pubmed]   

104.Alfieri A, Gardner C. The NK1 antagonist GR203040 inhibits cyclophosphamide-induced damage in the rat and ferret bladder. Gen Pharmacol 1997; 29:245-50.
http://dx.doi.org/10.1016/S0306-3623(96)00482-X


105.Deliveliotis C, Chrisofos M, Gougousis E, Papatsoris A, Dellis A, Varkarakis IM. Is there a role for alpha1-blockers in treating double-J stent-related symptoms? Urology 2006; 67:35-9.
http://dx.doi.org/10.1016/j.urology.2005.07.038
[
Pubmed]   

106.Dellabella M, Milanese G, Muzzonigro G. Efficacy of tamsulosin in the medical management of juxtavesical ureteral stones. J Urol 2003; 170:2202-5.
http://dx.doi.org/10.1097/01.ju.0000096050.22281.a7
[
Pubmed]   

107.Romics I. The role of alpha-adrenoreceptors in the treatment of urological diseases. Neurochem Int 2007; 51:328-31.
http://dx.doi.org/10.1016/j.neuint.2007.05.023
[
Pubmed]   

108.Trevisani M, Campi B, Gatti R, Andre E, Materazzi S, Nicoletti P, Gazzieri D, Geppetti P. The influence of alpha1-adrenoreceptors on neuropeptide release from primary sensory neurons of the lower urinary tract. Eur Urol 2007; 52:901-8.
http://dx.doi.org/10.1016/j.eururo.2007.01.016
[
Pubmed]   

109.Putoczki T, Ernst M. More than a sidekick: the IL-6 family cytokine IL-11 links inflammation to cancer. J Leukoc Biol 2010; 88:1109-17.
http://dx.doi.org/10.1189/jlb.0410226
[
Pubmed]   

110.Orazi A, Du X, Yang Z, Kashai M, Williams DA. Interleukin-11 prevents apoptosis and accelerates recovery of small intestinal mucosa in mice treated with combined chemotherapy and radiation. Lab Invest 1996; 75:33-42.
[
Pubmed]   

111.Trepicchio WL, Bozza M, Pedneault G, Dorner AJ. Recombinant human IL-11 attenuates the inflammatory response through down-regulation of proinflammatory cytokine release and nitric oxide production. J Immunol 1996; 157:3627-34.
[
Pubmed]   

112.Schwertschlag US, Trepicchio WL, Dykstra KH, Keith JC, Turner KJ, Dorner AJ. Hematopoietic, immunomodulatory and epithelial effects of interleukin-11. Leukemia 1999; 13:1307-15.
http://dx.doi.org/10.1038/sj.leu.2401514
[
Pubmed]   

113.Robb L, Dimitriadis E, Li R, Salamonsen LA. Leukemia inhibitory factor and interleukin-11: cytokines with key roles in implantation. J Reprod Immunol 2002; 57:129-41.
http://dx.doi.org/10.1016/S0165-0378(02)00012-8


114.Ciurea SO, Hoffman R. Cytokines for the treatment of thrombocytopenia. Semin Hematol 2007; 44:166-82.
http://dx.doi.org/10.1053/j.seminhematol.2007.04.005
[
Pubmed]   

115.Mota JM, Brito GA, Loiola RT, Cunha FQ, Ribeiro Rde A. Interleukin-11 attenuates ifosfamide-induced hemorrhagic cystitis. Int Braz J Urol 2007; 33:704-10.
http://dx.doi.org/10.1590/S1677-55382007000500013
[
Pubmed]   

116.Rubin JS, Osada H, Finch PW, Taylor WG, Rudikoff S, Aaronson SA. Purification and characterization of a newly identified growth factor specific for epithelial cells. Proc Natl Acad Sci USA 1989; 86:802-6.
http://dx.doi.org/10.1073/pnas.86.3.802


117.Yi ES, Williams ST, Lee H, Malicki DM, Chin EM, Yin S, Tarpley J, Ulich TR. Keratinocyte growth factor ameliorates radiation- and bleomycin-induced lung injury and mortality. Am J Pathol 1996; 149:1963-70.
[
Pubmed]    [PMC Free Fulltext]   

118.Farrell CL, Bready JV, Rex KL, Chen JN, DiPalma CR, Whitcomb KL, Yin S, Hill DC, Wiemann B, Starnes CO, Havill AM, Lu ZN, Aukerman SL, Pierce GF, Thomason A, Potten CS, Ulich TR, Lacey DL. Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality. Cancer Res 1998; 58:933-9.
[
Pubmed]   

119.Farrell CL, Rex KL Chen JN, Bready JV, DiPalma CR, Kaufman SA, Rattan A, Scully S, Lacey DL. The effects of keratinocyte growth factor inpreclinical models of mucositis. Cell Prolif 2002; 35(Suppl 1):78-85.
http://dx.doi.org/10.1046/j.1365-2184.35.s1.8.x
[
Pubmed]   

120.Barasch A, Epstein J, Tilashalski K. Palifermin for management of treatment-induced oral mucositis in cancer patients. Biologics 2009; 3:111-6.
http://dx.doi.org/10.2147/BTT.S3914
[
Pubmed]    [PMC Free Fulltext]   

121.Morais MM, Belarmino-Filho JN, Brito GA, Ribeiro RA. Pharmacological and histopathological study of cyclophosphamide-induced hemorrhagic cystitis - comparison of the effects of dexamethasone and Mesna. Braz J Med Biol Res 1999; 32:1211-5.
http://dx.doi.org/10.1590/S0100-879X1999001000006
[
Pubmed]   

122.Brock N, Stekar J, Pohl J, Niemeyer U, Scheffler G. Acrolein, the causative factor of urotoxic side-effects of cyclophosphamide, ifosfamide, trofosfamide and sufosfamide. Arzneimittelforschung 1979; 29:659-61.
[
Pubmed]   

123.Christophidis N, Cosolo W, Louis WJ, Louis CJ. The effect of penicillamine and related thiols on cyclophosphamide-induced cystitis and bone marrow suppression. Int J Tissue React 1984; 6:493-8.
[
Pubmed]   

124.Grinberg-Funes DJ, Sheldon C, Weiss M. The use of prostaglandin F2 alpha for the prophylaxis of cyclophosphamide induced cystitis in rats. J Urol 1990; 144:1500-4.
[
Pubmed]   

125.Kranc DM, Kim J, Straus F, Levine LA. Prophylactic and therapeutic carboprost tromethamine bladder irrigation in rats with cyclophosphamide-induced hemorrhagic cystitis. J Urol 1992; 148:1326-30.
[
Pubmed]   

126.Safron J, Rice D, Gordon D, Leaf C, White R. Protective effects of L-2-oxothiazolidine-4-carboxylate treatment on cyclophosphamide-induced cystitis in rats. J Urol 1997; 157:1946-50
http://dx.doi.org/10.1016/S0022-5347(01)64907-3


127.Assreuy AM, Martins GJ, Moreira ME, Brito GA, Cavada BS, Ribeiro RA, Flores CA. Prevention of cyclophosphamide-induced hemorrhagic cystitis by glucose-mannose binding plant lectins. J Urol 1999; 161:1988-93.
http://dx.doi.org/10.1016/S0022-5347(05)68870-2


128.Xu X, Malave A. Protective effect of berberine on cyclophosphamide-induced haemorrhagic cystitis in rats. Pharmacol Toxicol 2001; 88:232-7.
http://dx.doi.org/10.1034/j.1600-0773.2001.d01-109.x
[
Pubmed]   

129.Kobayashi M, Nomura M, Nishii H, Matsumoto S, Fujimoto N, Matsumoto T. Effect of eviprostat on bladder overactivity in an experimental cystitis rat model. Int J Urol 2008; 15:356-60.
http://dx.doi.org/10.1111/j.1442-2042.2008.01999.x
[
Pubmed]   

130.Vieira MM, Macedo FY, Filho JN, Costa AC, Cunha AN, Silveira ER, Brito GA, Ribeiro RA. Ternatin, a flavonoid, prevents cyclophosphamide and ifosfamide-induced hemorrhagic cystitis in rats. Phytother Res 2004; 18:135-41.
http://dx.doi.org/10.1002/ptr.1379
[
Pubmed]   

131.Alencar NM, Figueiredo IS, Vale MR, Bitencurt FS, Oliveira JS, Ribeiro RA, Ramos MV. Anti-inflammatory effect of the latex from Calotropis procera in three different experimental models: peritonitis, paw edema and hemorrhagic cystitis. Planta Med 2004; 70:1144-9.
http://dx.doi.org/10.1055/s-2004-835842
[
Pubmed]   

132.Abd-Allah AR, Gado AM, Al-Majed AA, Al-Yahya AA, Al-Shabanah OA. Protective effect of taurine against cyclophosphamide-induced urinary bladder toxicity in rats. Clin Exp Pharmacol Physiol 2005; 32:167-72.
http://dx.doi.org/10.1111/j.1440-1681.2004.04129.x
[
Pubmed]   

133.Topal T, Oztas Y, Korkmaz A, Sadir S, Oter S, Coskun O, Bilgic H. Melatonin ameliorates bladder damage induced by cyclophosphamide in rats. J Pineal Res 2005; 38:272-7.
http://dx.doi.org/10.1111/j.1600-079X.2004.00202.x
[
Pubmed]   

134.Hu VY, Zvara P, Dattilio A, Redman TL, Allen SJ, Dawbarn D, Stroemer RP, Vizzard MA. Decrease in bladder overactivity with REN1820 in rats with cyclophosphamide induced cystitis. J Urol 2005; 173:1016-21.
http://dx.doi.org/10.1097/01.ju.0000155170.15023.e5
[
Pubmed]   

135.Masuda H, Chancellor MB, Kihara K, Yoshimura N. 15-deoxy-Delta12,14-prostaglandin J2 attenuates development of cyclophosphamide-induced cystitis in rats. Urology 2006; 67:435-9.
http://dx.doi.org/10.1016/j.urology.2005.08.052
[
Pubmed]   

136.Sadir S, Deveci S, Korkmaz A, Oter S. Alpha-tocopherol, beta-carotene and melatonin administration protects cyclophosphamide-induced oxidative damage to bladder tissue in rats. Cell Biochem Funct 2007; 25:521-6.
http://dx.doi.org/10.1002/cbf.1347
[
Pubmed]   

137.Batista CK, Mota JM, Souza ML, Leitao BT, Souza MH, Brito GA, Cunha FQ, Ribeiro RA. Amifostine and glutathione prevent ifosfamide- and acrolein-induced hemorrhagic cystitis. Cancer Chemother Pharmacol 2007; 59:71-7.
http://dx.doi.org/10.1007/s00280-006-0248-z
[
Pubmed]   

138.Matsuoka Y, Masuda H, Yokoyama M, Kihara K. Protective effects of heme oxygenase-1 against cyclophosphamide-induced haemorrhagic cystitis in rats. BJU Int 2007; 100:1402-8.
http://dx.doi.org/10.1111/j.1464-410X.2007.07111.x
[
Pubmed]   

139.Chow YC, Yang S, Huang CJ, Tzen CY, Su YH, Wang PS. Prophylactic intravesical instillation of epinephrine prevents cyclophosphamide-induced hemorrhagic cystitis in rats. Exp Biol Med (Maywood) 2007; 232:565-70.
[
Pubmed]   

140.Korkmaz A, Kurt B, Yildirim I, Basal S, Topal T, Sadir S, Oter S. Effects of poly(ADP-ribose) polymerase inhibition in bladder damage caused by cyclophosphamide in rats. Exp Biol Med (Maywood) 2008; 233:338-43.
http://dx.doi.org/10.3181/0706-RM-151
[
Pubmed]   

141.Bhatia K, Ahmad F, Rashid H, Raisuddin S. Protective effect of S-allylcysteine against cyclophosphamide-induced bladder hemorrhagic cystitis in mice Food Chem Toxicol 2008; 46:3368-74.
http://dx.doi.org/10.1016/j.fct.2008.08.011
[
Pubmed]   

142.Ito K, Iwami A, Katsura H, Ikeda M. Therapeutic effects of the putative P2X3/P2X2/3 antagonist A-317491 on cyclophosphamide-induced cystitis in rats. Naunyn Schmiedebergs Arch Pharmacol 2008; 377:483-90.
http://dx.doi.org/10.1007/s00210-007-0197-z
[
Pubmed]   

143.Arafa HM. Uroprotective effects of curcumin in cyclophosphamide-induced haemorrhagic cystitis paradigm. Basic Clin Pharmacol Toxicol 2009; 104:393-9.
http://dx.doi.org/10.1111/j.1742-7843.2009.00379.x


144.Al-Yahya AA, Al-Majed AA, Gado AM, Daba MH, Al-Shabanah OA, Abd-Allah AR. Acacia Senegal gum exudate offers protection against cyclophosphamide-induced urinary bladder cytotoxicity. Oxid Med Cell Longev 2009; 2:207-13
http://dx.doi.org/10.4161/oxim.2.4.8878
[
Pubmed]    [PMC Free Fulltext]   

145.Abraham P, Rabi S, Kulothungan P. Aminoguanidine, selective nitric oxide synthase inhibitor, ameliorates cyclophosphamide-induced hemorrhagic cystitis by inhibiting protein nitration and PARS activation. Urology 2009; 73:1402-6.
http://dx.doi.org/10.1016/j.urology.2008.10.039
[
Pubmed]   

146.Sakura M, Masuda H, Matsuoka Y, Yokoyama M, Kawakami S, Kihara K. Rolipram, a specific type-4 phosphodiesterase inhibitor, inhibits cyclophosphamide-induced haemorrhagic cystitis in rats. BJU Int 2009; 103:264-9.
http://dx.doi.org/10.1111/j.1464-410X.2008.07948.x
[
Pubmed]   

147.Hamsa TP, Kuttan G. Protective role of Ipomoea obscura (L.) on cyclophosphamide-induced uro- and nephrotoxi-cities by modulating antioxidant status and pro-inflammatory cytokine levels. Inflammopharmacology 2011; 19:155-67.
http://dx.doi.org/10.1007/s10787-010-0055-3
[
Pubmed]   

148.Abraham P, Isaac B, Ramamoorthy H, Natarajan K. Oral Glutamine Attenuates Cyclophosphamide-Induced Oxidative Stress in the Bladder but Does Not Prevent Hemorrhagic Cystitis in Rats. J Med Toxicol 2011; 7:118-24.
http://dx.doi.org/10.1007/s13181-010-0103-9
[
Pubmed]   

149.Ayhanci A, Yaman S, Sahinturk V, Uyar R, Bayramoglu G, Senturk H, Altuner Y, Appak S, Gunes S. Protective effect of seleno-L-methionine on cyclophosphamide-induced urinary bladder toxicity in rats. Biol Trace Elem Res 2010; 134:98-108.
http://dx.doi.org/10.1007/s12011-009-8458-y
[
Pubmed]   

150.Santos AA Jr, Leal PC, Edelweiss MI, Lopes TG, Calixto JB, Morrone FB, Campos MM. Effects of the compounds MV8608 and MV8612 obtained from Mandevilla velutina in the model of hemorrhagic cystitis induced by cyclophosphamide in rats. Naunyn Schmiedebergs Arch Pharmacol 2010; 382:399-407.
http://dx.doi.org/10.1007/s00210-010-0555-0
[
Pubmed]   

151.Chuang YC, Tyagi P, Huang HY, Yoshimura N, Wu M, Kaufman J, Chancellor MB. Intravesical immune suppression by liposomal tacrolimus in cyclophosphamide-induced inflammatory cystitis. Neurourol Urodyn 2011; 30:421-7.
http://dx.doi.org/10.1002/nau.20981
[
Pubmed]   

152.Vera PL, Iczkowski KA, Howard DJ, Jiang L, Meyer-Siegler KL. Antagonism of macrophage migration inhibitory factor decreases cyclophosphamide cystitis in mice. Neurourol Urodyn 2010; 29:1451-7.
http://dx.doi.org/10.1002/nau.20878
[
Pubmed]   

153.Miki T, Matsunami M, Nakamura S, Okada H, Matsuya H, Kawabata A. ONO-8130, a selective prostanoid EP1 receptor antagonist, relieves bladder pain in mice with cyclophosphamide-induced cystitis. Pain 2011; 152:1373-81.
http://dx.doi.org/10.1016/j.pain.2011.02.019
[
Pubmed]   

154.Boeira VT, Leite CE, Santos AA Jr, Edelweiss MI, Calixto JB, Campos MM, Morrone FB. Effects of the hydroalcoholic extract of Phyllanthus niruri and its isolated compounds on cyclophosphamide-induced hemorrhagic cystitis in mouse. Naunyn Schmiedebergs Arch Pharmacol 2011; 384:265-75.
http://dx.doi.org/10.1007/s00210-011-0668-0
[
Pubmed]   

155.Martins J, Silva R, Coutinho-Silva R, Takiya C, Battastini A, Morrone F, Campos M. The role of P2X7 purinergic receptors in inflammatory and nociceptive changes accompanying cyclophosphamide-induced haemorrhagic cystitis in mice. Br J Pharmacol 2012; 165:183-96.
http://dx.doi.org/10.1111/j.1476-5381.2011.01535.x
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How to Cite this Article
Pubmed Style

Ribeiro RA, Lima-Junior RC, Leite CAV, Mota JMS, Macedo FY, Lima MV, Brito GA. Chemotherapy-induced hemorrhagic cystitis: pathogenesis, pharmacological approaches and new insights. J Exp Integr Med. 2012; 2(2): 95-112. doi:10.5455/jeim.080312.ir.010



Web Style

Ribeiro RA, Lima-Junior RC, Leite CAV, Mota JMS, Macedo FY, Lima MV, Brito GA. Chemotherapy-induced hemorrhagic cystitis: pathogenesis, pharmacological approaches and new insights. www.scopemed.org/?mno=13825 [Access: August 18, 2017]. doi:10.5455/jeim.080312.ir.010



AMA (American Medical Association) Style

Ribeiro RA, Lima-Junior RC, Leite CAV, Mota JMS, Macedo FY, Lima MV, Brito GA. Chemotherapy-induced hemorrhagic cystitis: pathogenesis, pharmacological approaches and new insights. J Exp Integr Med. 2012; 2(2): 95-112. doi:10.5455/jeim.080312.ir.010



Vancouver/ICMJE Style

Ribeiro RA, Lima-Junior RC, Leite CAV, Mota JMS, Macedo FY, Lima MV, Brito GA. Chemotherapy-induced hemorrhagic cystitis: pathogenesis, pharmacological approaches and new insights. J Exp Integr Med. (2012), [cited August 18, 2017]; 2(2): 95-112. doi:10.5455/jeim.080312.ir.010



Harvard Style

Ribeiro, R. A., Lima-Junior, R. C., Leite, C. A. V., Mota, J. M. S., Macedo, F. Y., Lima, M. V. & Brito, G. A. (2012) Chemotherapy-induced hemorrhagic cystitis: pathogenesis, pharmacological approaches and new insights. J Exp Integr Med, 2 (2), 95-112. doi:10.5455/jeim.080312.ir.010



Turabian Style

Ribeiro, Ronaldo A., Roberto C.P. Lima-Junior, Caio Abner V.G. Leite, Jose Mauricio S.C. Mota, Francisco Y.B. Macedo, Marcos V.A. Lima, and Gerly A.C. Brito. 2012. Chemotherapy-induced hemorrhagic cystitis: pathogenesis, pharmacological approaches and new insights. Journal of Experimental and Integrative Medicine, 2 (2), 95-112. doi:10.5455/jeim.080312.ir.010



Chicago Style

Ribeiro, Ronaldo A., Roberto C.P. Lima-Junior, Caio Abner V.G. Leite, Jose Mauricio S.C. Mota, Francisco Y.B. Macedo, Marcos V.A. Lima, and Gerly A.C. Brito. "Chemotherapy-induced hemorrhagic cystitis: pathogenesis, pharmacological approaches and new insights." Journal of Experimental and Integrative Medicine 2 (2012), 95-112. doi:10.5455/jeim.080312.ir.010



MLA (The Modern Language Association) Style

Ribeiro, Ronaldo A., Roberto C.P. Lima-Junior, Caio Abner V.G. Leite, Jose Mauricio S.C. Mota, Francisco Y.B. Macedo, Marcos V.A. Lima, and Gerly A.C. Brito. "Chemotherapy-induced hemorrhagic cystitis: pathogenesis, pharmacological approaches and new insights." Journal of Experimental and Integrative Medicine 2.2 (2012), 95-112. Print. doi:10.5455/jeim.080312.ir.010



APA (American Psychological Association) Style

Ribeiro, R. A., Lima-Junior, R. C., Leite, C. A. V., Mota, J. M. S., Macedo, F. Y., Lima, M. V. & Brito, G. A. (2012) Chemotherapy-induced hemorrhagic cystitis: pathogenesis, pharmacological approaches and new insights. Journal of Experimental and Integrative Medicine, 2 (2), 95-112. doi:10.5455/jeim.080312.ir.010