Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil
| dc.contributor.advisor1 | Valadares, Marize Campos | |
| dc.contributor.advisor1Lattes | http://lattes.cnpq.br/6157755243167018 | por |
| dc.contributor.referee1 | Martins, Manoela Domingues | |
| dc.contributor.referee2 | Marreto, Ricardo Neves | |
| dc.creator | Santos Filho, Edvande Xavier dos | |
| dc.creator.Lattes | http://lattes.cnpq.br/9106451112293396 | por |
| dc.date.accessioned | 2014-09-22T18:45:16Z | |
| dc.date.issued | 2014-03-20 | |
| dc.description.abstract | Introduction: Intestinal mucositis is a frequent limiting factor in antineoplastic therapy. There is no truly effective treatment targeted to cure this side effect. Curcuma longa L. has been reported to have antioxidant, antitumor and anti-inflammatory properties. Objective: This study aimed to evaluate the effects of a mucoadhesive formulation with Curcuma longa L. extract (MCL) in mice bearing intestinal mucositis induced by 5-FU. Methods: Swiss male adult mice (35-40g) were randomly allocated into three experimental groups of 5 animals each: control (mucoadhesive formulation 0.6mL/animal, via gavage, from day 1-6); exposed to 5-fluorouracil (5-FU 200mg/kg, i.p., in days 4-6); treated prophylactically and throughout mucositis with FMCL and exposed to 5-FU (MCL 15mg/kg, via gavage, from day 1-6, plus 5-FU 200mg/kg, i.p., in days 4-6). In the 7th day, animals were anesthetized by xylazine-ketamine followed by cervical dislocation. Duodenal samples, 10 cm after pyloric sphincter were removed to perform the essays. The parameters evaluated were: body weight assessment, morphometrics and histo-pathological analysis, apoptosis (p53/Bax, Bcl-2), cell proliferation (Ki-67), myelo-peroxidase (MPO) and malondialdehyde (MDA). Results: 5-FU induced intestinal mucositis characterized by villus shortening, crypt deepening, intense inflammatory infiltration, vacuolization and mucosal edema. Besides, 5-FU induced severe mice body mass reduction, apoptosis in cells of villus and crypts (p<0.001), increase in MPO activity and MDA formation (p<0.05), when compared to the control group. Treatment with MCL attenuated body mass loss, protected intestinal mucosa from villus shortening and crypt deepening, decrease MPO activity and MDA formation (p<0.05). In this group of animals was also observed high expression of the cell proliferation marker Ki-67 in epithelial cells lining of villus and crypts. Conclusion: Our data confirm the therapeutic potential of MCL for the treatment of intestinal mucositis in mice. Further studies are needed to assess this formulation potential for human use. | eng |
| dc.description.provenance | Submitted by Jaqueline Silva (jtas29@gmail.com) on 2014-09-22T17:08:11Z No. of bitstreams: 2 Santos Filho, Edvande-2014-dissertação.pdf: 3465269 bytes, checksum: fd50a85f70b6b596e0c5c4fb5fd18cb9 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) | eng |
| dc.description.provenance | Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2014-09-22T18:45:16Z (GMT) No. of bitstreams: 2 Santos Filho, Edvande-2014-dissertação.pdf: 3465269 bytes, checksum: fd50a85f70b6b596e0c5c4fb5fd18cb9 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) | eng |
| dc.description.provenance | Made available in DSpace on 2014-09-22T18:45:16Z (GMT). No. of bitstreams: 2 Santos Filho, Edvande-2014-dissertação.pdf: 3465269 bytes, checksum: fd50a85f70b6b596e0c5c4fb5fd18cb9 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-03-20 | eng |
| dc.description.resumo | Introdução: A mucosite intestinal é um dos efeitos adversos limitantes das terapias antineoplásicas. Não existe tratamento realmente efetivo direcionado a cura deste efeito colateral grave. A Curcuma longa L. tem sido proposta como candidata ao tratamento de várias doenças por possuir propriedades antioxidante, antitumoral e anti-inflamatória. Objetivo: Este estudo objetivou avaliar os efeitos da formulação mucoadesiva com extrato de Curcuma longa L. (FMCL) em animais portadores de mucosite intestinal induzida por 5-FU. Métodos: Camundongos Swiss adultos, machos (35-40g) foram aleatoriamente alocados em três grupos experimentais de 5 animais cada: [1] controle (formulação mucoadesiva 0.6mL/animal, via gavagem, do dia 1-6); [2] exposto ao 5-fluorouracil (5-FU 200mg/kg, i.p., dos dias 4-6), [3] tratado profilaticamente e ao curso da mucosite com FMCL e exposto ao 5-FU (FMCL 15mg/kg, via gavagem dos dias 1-6, mais 5-FU 200mg/kg, i.p., dos dias 4-6). No sétimo dia, os animais foram anestesiados por xilazina-ketamina seguido por deslocamento cervical. Amostras de duodeno, 10 cm após o esfíncter pilórico, foram coletadas para realização dos ensaios. Os parâmetros avaliados foram: avaliação de massa corporal, análise morfométrica e histopatológica, apoptose (p53/Bax; Bcl-2), proliferação celular (Ki-67), mieloperoxidase (MPO) e malondialdeído (MDA) Resultados: A administração de 5-FU induziu mucosite intestinal caracterizada por encurtamento das vilosidades, aprofundamento das criptas, intenso infiltrado infla-matório, vacuolização e edema na mucosa. Além disso, o 5-FU induziu grave redução de massa corporal nos camundongos e apoptose nas células das vilosida-des e criptas, quando comparado ao grupo controle (p<0,001). Foi observado ainda aumento na atividade de MPO e formação de MDA, quando comparado ao grupo controle (p<0,05). Por outro lado, o tratamento com a FMCL atenuou a perda de massa corporal dos animais com mucosite. Ademais, protegeu a mucosa intestinal da redução no tamanho das vilosidades e criptas induzidas pelo 5-FU. Neste grupo de animais foi observado ainda aumento na expressão do marcador de proliferação celular Ki-67 nas células epiteliais de revestimento das vilosidades e criptas intestinais. O tratamento também diminuiu significantemente a atividade de MPO e formação de MDA (p<0,05). Conclusão: Os dados confirmam o potencial terapêutico da FMCL no tratamento da mucosite intestinal em camundongos. Estudos adicionais são necessários para que esta formulação possa se tornar uma alternativa segura para uso em seres humanos. | por |
| dc.format | application/pdf | * |
| dc.identifier.citation | Santos Filho, Edvande Xavier dos. Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil. 2014. 90 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia. | por |
| dc.identifier.uri | http://repositorio.bc.ufg.br/tede/handle/tede/3114 | |
| dc.language | por | por |
| dc.publisher | Universidade Federal de Goiás | por |
| dc.publisher.country | Brasil | por |
| dc.publisher.department | Faculdade Farmácia - FF (RG) | por |
| dc.publisher.initials | UFG | por |
| dc.publisher.program | Programa de Pós-graduação em Ciências Farmacêuticas (FF) | por |
| dc.relation.references | AGGARWAL, B. B.; KUMAR, A.; BHARTI, A. C. Anticancer potencial of curcumin: Preclinical and clinical studies. Anticancer Research. v. 23, p. 363–398, 2003. AGGARWAL, B. B.; YUAN, W.; LI, S.; GUPTA, S. C. Multitargeting by turmeric, the golden spice: From kitchen to clinic. Molecular Nutrition & Food Research. v. 00, p. 1–14, 2013. AHSAN, H.; PARVEEN, N.; KHAN, N. U.; HADI, S. M. Pro-oxidant, antioxidant and cleavage activities on DNA of curcumin and its derivatives demethoxycurcumin and bisdemethoxycurcumin. Chemico-Biological Interactions. v. 121, p. 161–175, 1999. AK, T.; GÜLÇIN, I. Antioxidant and radical scavenging properties of curcumin. Chemico-Biological Interactions. p. 27–37, 2008. AL-BARRAK, J.; CHEUNG, W. Y. Adherence to imatinib therapy in gastrointestinal stromal tumors and chronic myeloid leukemia. Supportive Care in Cancer. DOI 10.1007/s00520-013-1831–6, 2013. ALDINI, R ; BUDRIESI, R ; RODA, G ; MICUCCI, M ; IOAN, P ; D’ERRICO-GRIGIONI, A.; SARTINI, A.; GUIDETTI, E.; MAROCCHI, M.; CEVENINI, M.; ROSINI, F.; MONTAGNANI, M.; CHIARINI, A.; MAZZELLA, G. Curcuma longa extract exerts a myorelaxant effect on the ileum and colon in a mouse experimental colitis model, independent of the anti-inflammatory effect. PLoS One. v. 7, n. 9, 2012. ALMEIDA, V. L.; LEITÃO, A.; REINA, L. C. B.; MONTANARI, C. A.; DONNICI, C. L. Câncer e agentes antineoplásicos ciclo-celular específicos e ciclo-celular não específicos que interagem com o DNA: uma introdução. Química Nova. v. 28, n. 1, p. 118–129, 2005. AMRUTAHERBALS. Disponível em: <http://www.amrutaherbals.com/specifications/ Haldi/Curcuma%20Longa.bmp>. Acesso em: 14 mar. 2013. ANAND, P.; KUNNUMAKKARA, A. B.; NEWMAN, R. A.; AGGARWAL, B. B. Bioavailability of Curcumin: Problems and Promises. Molecular Pharmaceutics. v. 4, p. 807–818, 2007. ANNADURAI, R. S.; NEETHIRAJ, R.; JAYAKUMAR, V.; DAMODARAN, A. C.; RAO, S. N.; KATTA, M. A.; GOPINATHAN, S.; SARMA, S. P.; SENTHILKUMAR, V.; NIRANJAN, V.; GOPINATH, A.; MUGASIMANGALAM, R. C. De Novo transcriptome assembly (NGS) of Curcuma longa L. rhizome reveals novel transcripts related to anticancer and antimalarial terpenoids. PLoS One. v. 8, n. 2, doi: 10.1371/ journal.pone.0056217, 2013. ANTO, R. J.; MUKHOPADHYAY, A.; DENNING, K.; AGGARWAL, B. B.; Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: its suppression by ectopic expression of Bcl-2 and Bcl-xl. Carcinogenesis. v. 23, p. 143–150, 2002. ANTUNES, L. M. G.; BIANCHINI, M. L. P. Antioxidantes da dieta como inibidores da nefrotoxicidade induzida pelo antitumoral cisplatina. Revista Nutrição. v. 17, p. 89–96, 2004. ANTUNES, S. A.; ROBAZZA, W. S.; SCHITTLER, L.; GOMES, G. A. Synergistic and antimicrobial properties of commercial turmeric (Curcuma longa) essential oil against pathogenic bacteria. Ciência e Tecnologia de Alimentos. v. 32, n. 3, p. 525–530, 2012. ANUCHAPREEDA, S.; LEECHANACHAIB, P.; SMITH, M. M.; AMBUDKAR, S. V.; LIMTRAKUL, P. Modulation of P-glycoprotein expression and function by curcumin in multidrug resistant human KB cells. Biochemical Pharmacology. v. 64, p. 573–582, 2002. APISARIYAKUL, A.; VANITTANAKOM, N.; BUDDHASUKH, D. Antifungal activity of turmeric oil extracted from Curcuma longa (Zingiberaceae). Journal of Ethnopharmacology. v. 49, p. 163–169, 1995. ARAUJO, C. A. C.; LEON, L. L. Biological activities of Curcuma longa L. Memórias do Instituto Oswaldo Cruz. v. 96, n. 5, p. 723–728, 2001. ASSERSOHN, L.; NORMAN, A. R.; CUNNINGHAM, D.; IVESON, T.; SEYMOUR, M.; HICKISH, T.; MASSEY, A.; PRIOR, Y.; HILL, M. E. A randomised study of protracted venous infusion of 5-fluorouracil (5-FU) with or without bolus mitomycin C (MMC) in patients with carcinoma of unknown primary. European Journal of Cancer. v. 39, n. 8, p. 1121–1128, 2003. BABU, P. S.; SRINIVASAN, K. Renal lesions in streptozotocin-induced diabetic rats maintened on onion and capsaicin containing diets. Journal of Nutrition Biochemistry. v. 10, p. 477–483, 1999. BALASUBRAMANYAM, M.; KOTESWARI, A. A.; KUMAR, R. S.; MONICKARAJ, S. F.; MAHESWARI, J. U.; MOHAN, V. Curcumin-induced inhibition of cellular reactive oxygen species generation: Novel therapeutic implications. Bioscience Journal. v. 28, p. 715–721, 2003. BASNET, P.; SKALKO-BASNET, N. Curcumin: An Anti-Inflammatory Molecule from a Curry Spice on the Path to Cancer Treatment. Molecules. v. 16, p. 4567-4598, 2011. BAYET-ROBERT, M.; MORVAN, D. Metabolomics reveals metabolic targets and biphasic responses in breast cancer cells treated by curcumin alone and in association with docetaxel. PLoS One. v. 8, n. 3, 2013. BECK, P. L.; WALLACE, J. L. Cytokines in inflammatory bowel disease. Mediators of Inflammation. v. 6, p. 95–103, 1997. BENZ, C.; DEGREGORIO, M.; SAKS, S.; SAMBOL, N.; HOLLERAN, W.; IGNOFFO, R.; LEWIS, B.; CADMAN, E. Sequential infusions of methotrexate and 5-fluorouracil in advanced cancer: pharmacology, toxicity, and response. Cancer Research. v. 45, n. 7, p. 3354–3358, 1985. BENZ, C.; TILLIS, T.; TATTELMAN, E.; CADMAN, E. Optimal schedule of metho-trexate and 5-fluorouracil in human breast cancer. Cancer Research. v. 42, n. 5, p. 2081–2086, 1982. BHAUMIK, S.; ANJUM, R.; RANGARAJ, N.; PARDHASARADHI, B. V.; KHAR, A. Curcumin mediated apoptosis in AK-5 tumor cells involves the production of reactive oxygen intermediates. FEBS Letters. v. 456, n. 2, p. 311–314, 1999. BHULLAR, K. S.; JHA, A.; YOUSSEF, D.; RUPASINGHE, H. P. V. Curcumin and Its Carbocyclic Analogs: Structure-Activity in Relation to Antioxidant and Selected Biological Properties. Molecules. v. 18, n. 5, p. 5389–5404, 2013. BOLSOVER, S. R.; HYAMS, J. S.; SHEPHARD, E. A.; WHITE, H. A.; WIEDEMANN, C. G. Cell Biology. John Wiley & Sons. Hoboken, New Jersey, 2004. BOWEN, J. M.; GIBSON, R. J.; CUMMINS, A. G.; KEEFE, D. M. K. Intestinal mucositis: the role of the Bcl-2 family, p53 and caspases in chemotherapy-induced damage. Supportive Care in Cancer. v. 14, n. 7, p. 713–731, 2006. BRADFORD, M. M. Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Analytical Biochemistry. v. 72, p. 248–254, 1976. BRADLEY, P. P.; CHRISTENSEN, R. D.; ROTHSTEIN, G. Cellular and extracellular myeloperoxidase in pyogenic inflammation. Blood. v. 60, n. 3, p. 618–622, 1982. BRANDAO, H. N.; DAVID, J. P.; COUTO, R. D.; NASCIMENTO, J. A. P.; DAVID, J. M. Química e farmacologia de quimioterápicos antineoplásicos derivados de plantas. Química Nova. v. 33, n. 6, p. 1359–1369, 2010. BRUSCHI, M. L.; JONES, D. S.; PANZERI, H.; GREMIÃO, M. P. D.; DE FREITAS, O.; LARA, E. H. G. Semisolid Systems Containing Propolis for the Treatment of Periodontal Disease: In Vitro Release Kinetics, Syringeability, Rheological, Textural, and Mucoadhesive Properties. Journal of Pharmaceutical Sciences. v. 96, p. 2074–2089, 2007. BRUSCHI, M. L. Desenvolvimento e caracterização de sistemas de liberação de própolis intrabolsa periodontal. 2006. 318f. Tese (Doutorado em Ciências Farmacêuticas) - Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, 2006. BRUSCHI, M. L.; PANZERI, H.; FREITAS, O.; LARA, E. H. G.; GREMIÃO, M. P. D. Sistemas de liberação de fármaco intrabolsa periodontal. Revista Brasileira de Ciências Farmacêuticas. v. 42, n. 1, p. 29–47, 2006. BULLWINKEL, J.; BARON-LÜHR, B.; LÜDEMANN, A.; WOHLENBERG, C.; GERDES, J.; SCHOLZEN, T. Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells. Journal of Cellular Physiology. v. 206, p. 624–635, 2006. CANCERBATTLEFIELD. Disponível em: <http://cancerbattlefield.com/wpcontent/ uploads/2009/05/turmeric-300x300.jpg>. Acesso em: 14 mar. 2013. CARNEIRO-FILHO, B. A.; LIMA, I. P.; ARAUJO, D. H.; CAVALCANTE, M. C.; CARVALHO, G. H.; BRITO, G. A.; LIMA, V.; MONTEIRO, S. M.; SANTOS, F. N.; RIBEIRO, R. A.; LIMA, A. A. Intestinal barrier function and secretion in methotrexate-induced rat intestinal mucositis. Digestive Diseases and Sciences. v. 49, n. 1, p. 65–72, 2004. CARNEIRO, M. L. B. Alterações morfológicas e estruturais induzidas por um componente do açafrão (Curcuma longa) em cultura de células de melanoma humano. 2007. 79p. Dissertação (Mestrado em Biologia), Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, 2007. CESCATO, V. A. S. Expressão dos genes relacionados à apoptose, Bcl-2, bax, e caspase-3 nos adenomas hipofisários clinicamente não funcionantes e seu potencial como marcador do comportamento tumoral. 2010. 95p. Tese (Doutorado em Ciências), Faculdade de Medicina, Universidade de São Paulo, São Paulo, 2010. CHAN, M. M. Inhibition of tumor necrosis factor by curcumina hytochemical. Biochemical Pharmacology. v. 49, n. 11, p. 1551–1556, 1995. CHAO, D. L.; SANCHEZ, C. A.; GALIPEAU, P. C.; BLOUNT, P. L.; PAULSON, T. G.; COWAN, D. S.; AYUB, K.; ODZE, R. D.; RABINOVITCH, P. S.; REID, B. J. Cell proliferation, cell cycle abnormalities, and cancer outcome in patients with Barrett's esophagus: a long-term prospective study. Clinical Cancer Research. v. 14, n. 21, p. 6988–6995, 2008. CHEN, C.; JOHNSTON, T. D.; JEON, H.; GEDALY, R.; MCHUGH, P. P.; BURKE, T. G.; RANJAN, D. An in vitro study of liposomal curcumin: Stability, toxicity and biological activity in human lymphocytes and Epstein-Barr virus-transformed human B-cells. International Journal of Pharmaceutics. v. 366, p. 133–139, 2009. CHEN, M. J.; CHENG, Y. M.; LAI, P. H.; WU, J. F.; HSU, Y. C. In vitro biocompatibility of thermally gelling liquid mucoadhesive loaded curcuminoids in colorectal cancer chemoprevention. International Journal of Colorectal Disease. v. 27, n. 7, p. 869–878, 2012. CHEN, V. L.; SURANA, N. K.; DUAN, J.; KASPER, D. L. Role of murine intestinal interleukin-1 receptor 1-expressing lymphoid tissue inducer-like cells in salmonella infection. PLoS One. v. 8, n. 6, DOI 10.1371/journal.pone. 0065405, 2013. CHIMABUCURO, W. K. Isquemia mesentérica e reposição do volume intravascular: Estudo comparativo entre duas soluções salinas com diferentes concentrações de cloreto de sódio nos eventos desencadeados pela reperfusão intestinal - Um modelo experimental em ratos. 2009. 96p. Tese (Doutorado em Ciências), Faculdade de Medicina, Universidade de São Paulo, São Paulo, 2009. CHINNA REDDY, P.; CHAITANYA, K. S.; MADHUSUDAN RAO, Y. A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods. DARU Journal of Pharmaceutical Sciences. v. 19, n. 6, p. 385–403, 2011. CHOWDHURY, J. U.; NANDI, N. C.; BHUIYAN, M. N. I.; MOBAROK, M. H. Essential oil constituents of the rhizomes of two types of Curcuma longa of Bangladesh. Bangladesh Journal of Scientific and Industrial Research. v. 43, p. 259–266, 2008. CRAIG, C. R.; STITZEL, R. E. Farmacologia moderna com aplicações clínicas. 6ª ed. Guanabara Koogan. Rio de Janeiro, 2005. 832p. CUNHA, F. L.; SILVA, C. M. G.; ALMEIDA, M. G.; LAMEIRO, T. M. M.; MARQUES, L. H. S.; MARGARIDO, N. F.; MARTINEZ, C. A. R. Reduction in oxidative stress levels in the colonic mucosa without fecal stream after the application of enemas containing aqueous Ilex paraguariensis extract. Acta Cirúrgica Brasileira. v. 26, n. 4, p. 289–296, 2011. DALZELL, J. R.; SAMUEL, L. M. The spectrum of 5-fluorouracil cardiotoxicity. Anticancer Drugs. v. 20, n. 1, p. 79–80, 2009. DI GIROLAMO, N.; VISVANATHAN, K.; LOYD, A.; WAKEFIELD, D. Expression of TNF-alpha by human plasma cells in chronic inflammation. Journal of Leukocyte Biology. v. 61, p. 667–678, 1997. DUMORTIER, G.; GROSSIORD, J. L.; AGNELY, F.; CHAUMEIL, J. C. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharmaceutical Research. v. 23, p. 2709–2728, 2006. DUNCAN, M.; GRANT, G. Oral and intestinal mucositis - causes and possible treatments. Alimentary Pharmacology & Therapeutics. v. 18, n. 9, p. 853–874, 2003. DUTTA, S.; PADHYE, S.; PRIYADARSINI, K. I.; NEWTON, C. Antioxidant and antiproliferative activity of curcumin semicarbazone. Bioorganic Medicinal Chemistry Letters. v. 15, p. 2738–2744, 2005. EPSTEIN, J.; SANDERSON, I. R.; MACDONALD, T. T. Curcumin as a the therapeutic agent: the evidence from in vitro, animal and human studies. British Journal of Nutrition. v. 103, p. 1545–1557, 2009. EUTAMENE, H.; THEODOROU, V.; VERGNOLLE, N.; COMERA, C.; FIORAMONTI, J.; BUENO, L. Involvement of interleukin-1, prostaglandins and mast cells in rectal distension-induced colonic water secretion in rats. The Journal of Physiology. v. 506, n. 1, p. 245–252, 1998. FARIA, M. H. G.; PATROCÍNIO, R. M. S. V.; FILHO, M. O. M.; RABENHORST, S. H. B. Expressão das proteínas BCL-2 e BAX em tumores astrocíticos humanos. Jornal Brasileiro de Patologia e Medicina Laboratorial. v. 42, n. 4, p. 271–278, 2006. FERREIRA, T. M.; LEONEL, A. J.; MELO, M. A.; SANTOS, R. R.; CARA, D. C.; CARDOSO, V. N.; CORREIA, M. I.; ALVAREZ-LEITE, J. I. Oral supplementation of butyrate reduces mucositis and intestinal permeability associated with 5-Fluorouracil administration. Lipids. v. 47, n. 7, p. 669–678, 2012. FIJLSTRA, M.; TISSING, W. J.; STELLAARD, F.; VERKADE, H. J.; RINGS, E. H. Reduced absorption of long-chain fatty acids during methotrexate-induced gastrointestinal mucositis in the rat. Clinical Nutrition. v. 32, n. 3, p. 452–459, 2013. FIOCCHI, C. Intestinal inflammation: a complex interplay of immune and nonimmune cell interactions. American Journal of Physiology. v. 273, p. 769–775, 1997. FIORUCCI, S.; MELI, R.; BUCCI, M.; CIRINO, G. Dual inhibitors of cyclooxygenase and 5-lipoxygenase. A new avenue in anti-inflammatory therapy? Biochemical Pharmacology. v. 62, p. 1433–1438, 2001. FISHER, T. C.; MILNER, A. E.; GREGORY, C. D.; JACKMAN, A. L.; AHERNE, G. W.; HARTLEY, J. A.; DIVE, C.; HICKMAN, J. A. bcl-2 modulation of apoptosis induced by anticancer drugs: resistance to thymidylate stress is independent of classical resistance pathways. Cancer Research. v. 53, n. 14, p. 3321–3326, 1993. FLECKNELL, P. Laboratory Animal Anaesthesia. 2ª edição. New York. Academic Press. p. 15–73 and p. 75-101, 1996. FUJISAWA, S.; ATSUMI, T.; ISHIHARA, M.; KADOMA, Y. Cytotoxicity, reactive oxygen species-generation activity and radical scavenging activity of curcumin and other related compounds. Anti-Cancer Research. v. 24, p. 563–570, 2004. GARDINER, K. R.; ANDERSON, N. H.; ROWLANDS, B. J.; BARBUL, A. Colitis and colonic mucosal barrier dysfunction. Gut. v. 37, p. 530–535, 1995. GIBSON, R. J.; BOWEN, J. M.; CUMMINS, A. G.; KEEFE, D. M. K. Relationship between dose of methotrexate, apoptosis, p53/p21 expression and intestinal crypt proliferation in the rat. Clinical and Experimental Medicine. v. 4, p. 188–195, 2005. GIERA, M.; LINGEMAN, H.; NIESSEN, W. M. Recent Advancements in the LC- and GC-Based Analysis of Malondialdehyde (MDA): A Brief Overview. Chromato-graphia. v. 75, p. 433-440, 2012. GOEL, A.; KUNNUMAKKARA, A B ; AGGARWAL, B B Curcumin as “curecumin” From kitchen to clinic. Biochemistry Pharmacology. v. 75, p. 787–809, 2008. GROBHOLZ, R.; ZENTGRAF, H.; KÖHRMANN, K. U.; BLEYL, U. Bax, Bcl-2, fas and Fas-L antigen expression in human seminoma: correlation with the apoptotic index. APMIS. v. 110, n. 10, p. 724-732, 2002. GROTZ, M. R. W.; DEITCH, E. A.; DING, J.; XU, D.; HUANG, Q.; REGEL, G. Intestinal Cytokine Response After Gut Ischemia. Role of Gut Barrier Failure. Annals of Surgery. v. 229, p. 478–486, 1999. GUPTA, S. C.; SUNG, B.; KIM, J. H.; PRASAD, S.; LI, S.; AGGARWAL, B. B. Multitargeting by turmeric, the golden spice: From kitchen to clinic. Molecular Nutrition & Food Research. v. 00, p. 1–19, 2012. GUTIERRES, V. O. Avaliação dos efeitos fisiológicos e bioquímicos do tratamento com curcumina incorporada ao iogurte na diabetes experimental. 2011. 120p. Dissertação (Mestrado em Biociências e Biotecnologia), Faculdade de Ciências Farmacêuticas, Universidade Estadual “Julio Mesquita Filho”, Araraquara, 2011. HADAR, T.; SHVERO, J.; YANIV, E.; RAM, E.; SHVILI, I.; KOREN, R. Expression of p53, ki-67 and bcl-2 in parathyroid adenoma and residual normal tissue. Pathology and Oncology Research. v. 11, p. 45–49, 2005. HAN, D. S.; LI, F.; HOLT, L.; CONNOLLY, K.; HUBERT, M.; MICELI, R.; OKOYE, Z.; SANTIAGO, G.; WINDLE, K.; WONG, E.; SARTOR, R. B. Keratinocyte growth factor-2 (FGF-10) promotes healing of experimental small intestinal ulceration in rats. American Journal of Physiology - Gastrointestinal and Liver Physiology. v. 279, p. 1011–1022, 2000. HAN, X.; WU, Z.; DI, J.; PAN, Y.; ZHANG, H.; DU, Y.; CHENG, Z.; JIN, Z.; WANG, Z.; ZHENG, Q.; ZHANG, P.; WANG, Y. CXCL9 attenuated chemotherapy-induced intestinal mucositis by inhibiting proliferation and reducing apoptosis. Biomedicine & Pharmacotherapy. v. 65, n. 8, p. 547–554, 2011. HANADA, M.; DELIA, D.; AIELLO, A.; STADTMAUER, E.; REED, J. C. bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood. v. 82, n. 6, p. 1820–1828, 1993. HENROTIN, Y.; PRIEM, F.; MOBASHERI, A. Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management. Springerplus. v. 2, n. 1, 2013. HERRSTEDT, J. Prevention and management of mucositis in patients with cancer. International Journal of Antimicrobial Agents. v. 16, p. 161–163, 2000. HOWARTH, G. S.; FRANCIS G. L.; COOL, J. C.; XU, X.; BYARD, R. W.; READ L. C. Milk growth factors enriched from cheese whey ameliorate intestinal damage by methotrexate when administered orally to rats. Journal of Nutrition. v. 126, p. 2519–2530, 1996. HUANG, M. T.; LOU, R. Y.; XIE, J. G.; MA, W.; LU, Y. P.; YEN, P.; ZHU, B. T.; NEWMARK, H.; HO, C. T. Effect of dietary curcumin and dibenzoylmethane on formation of 7,12-dimethylbez[a] anthracene-induced mammary tumors and lymphomas/leukemias in sencar mice. Carcinogenesis. v. 19, p. 1697–1700, 1998. HUANG, Y.; LEOBANDUNG, W.; FOSS, A.; PEPPAS, N. A. Molecular aspects of muco- and bioadhesion: tethered structures and site-specic surfaces. Journal of Controlled Release. v. 65, n. 1-2, p. 63–71, 2000. INSTITUTO NACIONAL DE CÂNCER – INCA. Ministério da Saúde, 2006. A Situação do Câncer no Brasil. Rio de Janeiro, 2006. 119p. Disponível em: <http://www.inca.gov.br/enfermagem/docs/cap1.pdf>. Acesso em: 22 mar. 2013. INSTITUTO NACIONAL DE CÂNCER – INCA. Ministério da Saúde, 2011. Coordenação Geral de Ações Estratégicas. Coordenação de Prevenção e Vigilância. Estimativa 2012: incidência de câncer no Brasil. Disponível em: <http://www. inca.gov.br/estimativa/2012/estimativa20122111.pdf>. Acesso em: 23 mar. 2013. INTERNATIONAL UNION AGAINST CANCER – UICC, 2006. Access to Cancer Drugs: A UICC position paper Revision 2008/09. Disponível em: <http://www. uicc.org/access-cancer-drugs-uicc-position-paper-revision-200809>. Acesso em: 22 mar. 2013. IRESON, C. R.; JONES, D. J. L.; ORR, S.; COUGHTRIE, M. W. H.; BOOCOCK, D. J.; WILLIAMS, M. L.; FARMER, P. B.; STEWARD, W. P.; GESCHER, A. J. Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiology Biomarkers Prevention. v. 11, p. 105–111, 2002. JAKOB, C.; LIERSCH, T.; MEYER, W.; BECKER, H.; BARETTON, G. B.; AUST, D. E. Predictive value of Ki67 and p53 in locally advanced rectal cancer: correlation with thymidylate synthase and histopathological tumor regression after neoadjuvant 5-FU-based chemoradiotherapy. World Journal of Gastroenterology. v. 14, n. 7, p. 1060-1066, 2008. JIANG, J. L.; JIN, X. L.; ZHANG, H.; SU, X.; QIAO, B.; YUAN, Y. J. Identification of antitumor constituents in curcuminoids from Curcuma longa L. based on the composition-activity relationship. Journal of Pharmaceutical and Biomedical Analysis. v. 70, p. 664–670, 2012. JONES, D. S.; BRUSCHI, M. L.; DE FREITAS, O.; GREMIÃO, M. P. D.; LARA, E. H. G.; ANDREWS, G. P. Rheological, mechanical and mucoadhesive properties of thermoresponsive, bioadhesive binary mixtures composed of poloxamer 407 and carbopol 974P designed as platforms for implantable drug delivery systems for use in the oral cavity. International Journal of Pharmaceutics. v. 372, p. 49–58, 2009. JUNQUEIRA, L. C. & CARNEIRO, J. Histologia Básica. 9ª ed. Guanabara Koogan. Rio de Janeiro, 1999. 524p. JUSTINO, P. F. C. Saccharomyces boulardii reverte a resposta inflamatória e funcional presente na mucosite intestinal induzida por 5-fluorouracil em camundongos. 2011. 89p. Dissertação (Mestrado em Farmacologia), Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2011. KAGNOFF, M. F.; ECKMANN, L. Epithelial cells as sensors for microbial infection. The Journal of Clinical Investigation. v. 100, n. 1, p. 259–263, 1997. KALPANA, C.; RAJASEKHARAN, K. N.; MENON, V. P. Modulatory effects of curcumin and curcumin analog on circulatory lipid profiles during nicotine-induced toxicity in wistar rats. Journal of Medicinal Food. v. 8, p. 246–250, 2005. KANAI, M.; OTSUKA, Y.; OTSUKA, K.; SATO, M.; NISHIMURA, T.; MORI, Y.; KAWAGUCHI, M.; HATANO, E.; KODAMA, Y.; MATSUMOTO, S.; MURAKAMI, Y.; IMAIZUMI, A.; CHIBA, T.; NISHIHIRA, J.; SHIBATA, H. A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin®) in cancer patients. Cancer Chemotherapy and Pharmacology. v. 71, n. 6, p. 1521–1530, 2013. KANITKAR, M.; GOKHALE, K.; GALANDE, S.; BHONDE, R. R. Novel role of curcumin in the prevention of cytokine-induced islet death in vitro and diabetogenesis in vivo. British Journal of Pharmacology. v. 155, p. 702–713, 2008. KATZUNG, B. G. Farmacologia Básica e Clínica. 10ª ed. Lange. São Paulo, 2007. 1060p. KEEFE, D. M. K.; CUMMINS, A. G.; DALE, B. M.; KOTASEK, D.; ROBB, T. A.; SAGE, R. E. Effect of high-dose chemotherapy on intestinal permeability in humans. Clinical Science. v. 92, p. 385–389, 1997. KEEFE, D. M.; SCHUBERT, M. M.; ELTING, L. S.; SONIS, S. T.; EPSTEIN, J. B.; RABER-DURLACHER, J. E.; MIGLIORATI, C. A.; MCGUIRE, D. B.; HUTCHINS, R. D.; PETERSON, D. E. Mucositis Study Section of the Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology: Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer. v. 109, p. 820–831, 2007. KERR, J. F.; WYLLIE, A. H.; CURRIE, A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. British Journal of Cancer. v. 26, n. 4, p. 239–257, 1972. KHAIR, O. A.; DAVIES, R. J.; DEVALIA, J. L. Bacterial-induced release of inflammatory mediators by bronchial epithelial cells. European Respiratory Journal. v. 9, n. 9, p. 1913–1922, 1996. KHUTORYANSKIY, V. V. Advances in mucoadhesion and mucoadhesive polymers. Macromolecular Bioscience. v. 11, p. 748–764, 2011. KIM, M.; KIM, Y. Hypocholesterolemic effects of curcumin via up-regulation of cholesterol 7a-hydroxylase in rats fed a high fat diet. Nutrition Research and Practice. v. 4, n. 3, p. 191–195, 2010. KIM, Y. A.; CHUNG, H. C.; CHOI, H. J.; RHA, S. Y.; SEONG, J. S.; JEUNG, H. C. Intermediate dose 5-fluorouracil-induced encephalopathy. Japanese Journal of Clinical Oncology. v. 36, n. 1, p. 55–59, 2006. KISSOW, H.; VIBY, N. E.; HARTMANN, B.; HOLST, J. J.; TIMM, M.; THIM, L.; POULSEN, S. S. Exogenous glucagon-like peptide-2 (GLP-2) prevents chemotherapy-induced mucositis in rat small intestine. Cancer Chemotherapy and Pharmacology. v. 70, n. 1, p. 39–48, 2012. KLESNEY-TAIT, J.; KECK, K.; LI, X.; GILFILLAN, S.; OTERO, K.; BARUAH, S.; MEYERHOLZ, D. K.; VARGA, S. M.; KNUDSON, C. J.; MONINGER, T. O.; MORELAND, J.; ZABNER, J.; COLONNA M. Transepithelial migration of neutrophils into the lung requires TREM-1. Journal of Clinical Investigation. v. 123, n. 1, p. 138–149, 2013. KUAN, C. Y.; ROTH, K. A.; FLAVELL, R. A.; RAKIC, P. Mechanisms of programmed cell death in the developing brain. Trends in Neurosciences. v. 23, p. 291–297, 2000. KUHN, A. Aplicação do laser de baixa intensidade no tratamento da mucosite oral induzida por quimioterapia e/ou radioterapia. 2007, 140p. Dissertação (Mestrado em Ciências Médicas), Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, 2007. KUNCHANDY, E.; RAO, M. N. A. Oxygen radical scavenging activity of curcumin. Journal of Pharmacology. v. 58, p. 237–240, 1990. KUWABARA, N.; TAMADA, S.; IWAI, T.; TERAMOTO, K.; KANEDA, N.; YUKIMURA, T.; NAKATANI, T.; MIURA, K. Attenuation of renal fibrosis by curcumin in rat obstructive nephropathy. Urology. v. 67, p. 440–446, 2006. LAO, C. D.; RUFFIN, M. T.; NORMOLLE, D.; HEATH, D. D.; MURRAY, S. I.; BAILEY, J. M.; BOGGS, M. E.; CROWELL, J.; ROCK, C. L.; BRENNER, D. E. Dose escalation of a curcuminoid formulation. BMC, Complementary and Alternative Medicine. v. 6, p. 10, 2006. LEE, H. S. Antiplatelet property of Curcuma longa L. rhizome-derived ar-turmerone. Bioresource Technology. v. 97, n. 12, p. 1372–1376, 2006. LEE, H. S.; LI, L.; KIM, H. K.; BILEHAL, D.; LI, W.; LEE, D. S.; KIM, Y. H. The protective effects of Curcuma longa Linn. extract on carbon tetrachloride-induced hepatotoxicity in rats via upregulation of Nrf2. Journal of Microbiology and Biotechnology. v. 20, n. 9, p. 1331–1338, 2010. LENGYEL, E.; SAWADA, K.; SALGIA, R. Tyrosine Kinase mutations in human cancer. Current Molecular Medicine. v. 7, p. 77–84, 2007. LETCHFORD, K.; LIGGINS, R.; BURT, H. Solubilization of hydrophobic drugs by methoxy poly(ethylene glycol)-block-polycaprolactone diblock copolymer micelles: Theoretical and experimental data and correlations. Journal Pharmaceutical Science. v. 96, n. 3, 2007. LI, F.; ZHAO, C.; WANG, L. Molecular targeted agents (MTA) combination therapy for cancer: Developments and potentials. International Journal of Cancer. DOI: 10.1002/ijc.28261, 2013. LI, S. Y.; YUAN, W.; DENG, G. R.; WANG, P.; YANG, P.; AGGARWAL, B. B. Chemical composition and product quality control of turmeric (Curcuma longa L.). Pharmaceutical Crops. v. 2, p 28–54, 2011. LI, X.; MARANI, M.; MANNUCCI, R.; KINSEY, B.; ANDRIANI, F.; NICOLETTI, I.; DENNER, L.; MARCELLI, M. Overexpression of BCL-X(L) underlies the molecular basis for resistance to staurosporine-induced apoptosis in PC-3 cells. Cancer Research. v. 61, p. 1699–1706, 2001. LIMA, V. Evidências da participação de TNF-α e COX-2 nas mucosites oral e intestinal induzidas por 5-fluorouracil e metotrexato em animais. 2004, 212p. Tese (Doutorado em Farmacologia), Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2004. LINHARES, S.; GEWANDDSZNAJDER, F. Biologia Hoje. 14ª ed. Ática. São Paulo, 2005. 696p. LINK, A.; BALAGUER, F.; SHEN, Y.; LOZANO, J. J.; LEUNG, H. C.; BOLAND, C. R.; GOEL, A. Curcumin modulates DNA methylation in colorectal cancer cells. PLoS One. v. 8, n. 2, 2013. LONGLEY, D. B.; HARKIN, D. P.; JOHNSTON, P. G. 5-Fluorouracil: mechanisms of action and clinical strategies. Cancer. v. 3, p. 330–338, 2003. MA, Z.; SHAYEGANPOUR, A.; BROCKS, D. R.; LAVASANIFAR, A.; SAMUEL, J. High-performance liquid chromatography analysis of curcumin in rat plasma: application to pharmacokinetics of polymeric micellar formulation of curcumin. Biomedical Chromatography. v. 21, n. 5, p. 546–552, 2007. MADARA, J. L.; PATAPOFF, T. W.; GILLECE-CASTRO, B.; COLGAN, S. P.; PARKOS, C. A.; DELP, C.; MRSNY, R. J. 5'-AMP is the neutrophil derived paracrine factor that ilicits chloride secretion from T84 epithelial monolayers. The Journal of Clinical Investigation. v. 91, p. 2320–2325, 1993. MAHESHWARI, R. K.; SINGH, A. K.; GADDIPATI, J.; SRIMAL, R. C. Multiple biological activities of curcumin: a short review. Life Sciences. v. 78, p. 2081–2087, 2006. MAITI, K.; MUKHERJEE, K.; GANTAIT, A.; SAHA, B. P.; MUKHERJEE, P. K. Curcumin–phospholipid complex: Preparation, therapeutic evaluation and pharmacokinetic study in rats. International Journal of Pharmaceutics. v. 330, n. 1, p. 155–163, 2007. MARINI, H.; ALTAVILLA, D.; BELLOMO, M.; ADAMO, E. B.; MARINI, R.; LAUREANTI, F.; BONACCORSO, M. C.; SEMINARA, P.; PASSANITI, M.; MINUTOLI, L.; BITTO, A.; CALAPAI, G.; SQUADRITO, F. Modulation of IL-1 beta gene expression by lipid peroxidation inhibition after kainic acid-induced rat brain injury. Experimental Neurology. v. 188, p. 178–186, 2004.MARQUES, L. H. S.; SILVA, C. M. G.; LAMEIRO, T. M. M.; ALMEIDA, M. G.; CUNHA, F. L.; PEREIRA, J. A.; MARTINEZ, C. A. R. Avaliação dos Níveis de Peroxidação Lipídica em Células da Mucosa Cólica após Aplicação de Enemas com Peróxido de Hidrogênio. Estudo Experimental em Ratos. Revista Brasileira de Coloproctologia. v. 30, n. 3, p. 272–280, 2010. MAZUMDER, A.; WANG, S.; NEAMATI, N.; NICKLAUS, M.; SUNDER, S.; CHEN, J.; MILNE, G. W. A.; RICE, W. G.; JR, T. R. B.; POMMIER, Y. Antiretroviral agents inhibitors of both human immunodeficiency virus type 1 integrase and protease. Journal of Medicinal Chemistry. v. 39, p. 2472–2481, 1996. MILLER, M. M; DONALD, V. D; HAGEMANN, M. T. Prevetion and treatment of oral mucositis in children with cancer. The journal of Pediatric Pharmacology and Therapeutics. v. 17, n. 4, p. 340–350, 2012. MILKS, L. C.; BRONTOLI, M. J.; CRAMER, E. B. Epithelial permeability and the transepithelial migration of human neutrophils. The Journal of Cell Biology. v. 96, p. 1241–1247, 1983. MISODOR. Disponível em: <http://www.misodor.com/images/5h66j78k.jpg>. Acesso em: 17 mar. 2013. MORTAZAVI, S. An in vitro assessment of mucus/mucoadhesive interaction. International Journal of Pharmaceutics. v. 124, p.173–182, 1995. MYTHRI, R. B.; BHARATH, M. M. Curcumin: a potential neuroprotective agent in Parkinson's disease. Current Pharmaceutical Design. v. 18, p. 91–99, 2012. NAKSURIYA, O.; OKONOGI, S.; SCHIFFELERS, R.M.; HENNINK, W. E. Curcumin nanoformulations: A review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment. Biomaterials. v. 35, n. 10, p. 3365–3383, 2014. NANDAKUMAR, D. N.; NAGARAJ, V. A.; VATHSALA, P. G.; RANGARAJAN, P.; PADMANABAN, G. Curcumin-artemisin combination therapy for malaria. Antimicrobial Agents and Chemotherapy. v. 50, p. 1859–1860, 2006. NASH, S.; STAFFORD, J.; MADARA, J. L. Effects of polymorphonuclear leukocyte transmigration on barrier function of cultured intestinal epithelial monolayers. The Journal of Clinical Investigation. v. 80, p. 1104–1113, 1987. NAZ, S.; JABEEN, S.; ILYAS, S.; MANZOOR, F.; ASLAM, F.; ALI, A. Antibacterial activity of Curcuma longa varieties against different strains of bacteria. Pakistan Journal of Botany. v. 42, p. 455–462, 2010. NEGRI, P. S.; JAYAPRAKASHA, G. K.; RAO, L. J. M.; SAKARIAH, K. K. Antibacterial activity of turmeric oil: A byproduct from Curcumin manufacture. Agricultural and Food Chemistry. v. 47, p. 4297–4300, 2005. NISHIYAMA, T.; MAE, T.; KISHIDA, H.; TSUKAGAWA, M.; MIMAKI, Y.; KURODA, M.; SASHIDA, Y.; TAKAHASHI, K.; KAWADA, T.; NAKAGAWA, K.; KITAHARA, M. Curcuminoids and sesquiterpenoids in turmeric (Curcuma longa L.) suppress an increase in blood glucose level in type 2 diabetic KK-Ay mice. Journal of Agricultural and Food Chemistry. v. 53, n. 4, p. 959–963, 2005. NOTOYA, M.; NISHIMURA, H.; WOO, J.; NAGAI, K.; ISHIHARA, Y.; HAGIWARA, H. Curcumin inhibitis the proliferation and mineralization of cultured osteoblasts. Journal Pharmacology. v. 534, p. 55–62, 2006. NUSRAT, A.; PARKOS, C. A.; LIANG, T. W.; CARNES, D. K.; MADARA, J. L. Neutrophil migration across model intestinal epithelia: monolayer disruption and subsequent events in epithelial repair. Gastroenterology. v. 113, p. 1489–1500, 1997. OECD 420. Disponível em: <http://www.oecd.org/chemicalsafety/risk-assessment/19 48362.pdf>. Acesso em: 22 jun. 2013. OHKAWA, H.; OHISHI, Í.; YAGI, Ê. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry. v. 95, p. 351–358, 1979. OKADA, K.; WANGPOENGTRAKUL, C.; TANAKA, T.; TOYOKUNI, S.; UCHIDA, K.; OSAWA, T. Curcumin and especially tetrahydrocurcumin ameliorate oxidative stress induced renal injury in mice. Journal of Nutrition. v. 31, p. 2090–2095, 2001. OLSZANECKI, R.; JAWIEN, J.; GAJDA, M.; MATEUSZUK, L.; GEBSKA, A.; KORABIOWSKA, M.; CHLOPICKI, S.; KORBU, R. Effect of curcumin on atherosclerosis in apoE/ LDL-R double knockout mice. Journal of Physiology and Pharmacology. v. 56, p. 627–635, 2005. PARK, S. Y.; KIM, Y. H.; KIM, Y.; LEE, S. J. Aromatic-turmerone's anti-inflammatory effects in microglial cells are mediated by protein kinase A and heme oxygenase-1 signaling. Neurochemistry International. v. 61, n. 5, p. 767–777, 2012. PARKIN, J.; COHEN, B. An overview of the immune system. Immunology. v. 357, n. 2, p. 1777–1789, 2001. PARSONS, P. E.; SUGAHARA, K.; COTT, G. R.; MASON, R. J.; HENSON, P. M. The effect of neutrophil migration and prolonged neutrophil contact on epithelial permeability. American Journal of Pathology. v. 129, p. 302–312, 1987. PATEL, H. R.; PATEL, R. P.; PATEL, M. M. Poloxamers: A pharmaceutical excipients with therapeutic behaviors. International Journal of PharmTech Research. v. 1, n. 2, p. 299–303, 2009. PENALOZA, C.; ORLANSKI, S.; YE, Y.; ENTEZARI-ZAHER, T.; JAVDAN, M.; ZAKERI, Z. Cell death in mammalian development. Current Pharmaceutical Design. v. 14, p. 184–196, 2008. PETERS, B. M.; JABRA-RIZK, M. A.; O'MAY, G. A.; COSTERTON, J. W.; SHIRTLIFF, M. E. Polymicrobial interactions: impact on pathogenesis and human disease. Clinical Microbiology Reviews. v. 25, n. 1, p. 193–213, 2012. PEREZ-ARRIAGA, L.; MENDOZA-MAGAÑA, M. L.; CORTÉS-ZÁRATE, R.; CORONA-RIVERA, A.; BOBADILLA-MORALES, L.; TROYO-SANROMÁN, R.; RAMÍREZ-HERRERA, M. A. Cytotoxic effect of curcumin on Giardia lamblia trophozoites. Acta Tropica. v. 98, p. 152–161, 2006. PRAKOBWONG, S.; GUPTA, S. C.; KIM, J. H.; SUNG, B.; PINLAOR, P.; HIRAKU, Y.; WONGKHAM, S.; SRIPA, B.; PINLAOR, S.; AGGARWAL, B. B. Curcumin suppresses proliferation and induces apoptosis in human biliary cancer cells through modulation of multiple cell signaling pathways. Carcinogenesis. v. 32, p. 1372–1380, 2011. PRITCHARD, D. M.; POTTEN, C. S.; HICKMAN, J. A. The relationships between p53-dependent apoptosis, inhibition of proliferation, and 5-fluorouracil-induced histopathology in murine intestinal epithelia. Cancer Research. v. 58, n. 23, p. 5453–5465, 1998. RAJASEKARAN, S. A. Therapeutic potential of curcumin in gastrointestinal diseases. World Journal of Gastrointestinal Pathophysiology. v. 2, n. 1, p. 1–14, 2011. RAMSEWAK, R. S.; DeWITT, D. L.; NAIR, M. G. Cytotoxicity, antioxidant and anti-inflammatory activities of Curcumins I-III from Curcuma longa. Phytomedicine. v. 7, n. 4, p. 303–308, 2000. RINGMAN, J. M.; FRAUTSCHY, S. A.; COLE, G. M.; MASTERMAN, D. L.; CUMMINGS, J L A potential role of the curry spice curcumin in alzheimer’s disease Current Alzheimer Research. v. 2, 2005. ROBHOLZ, R.; ZENTGRAF, H.; KÖHRMANN, K. U.; BLEYL, U. Bax, Bcl-2, fas and Fas-L antigen expression in human seminoma: correlation with the apoptotic index. APMIS. v. 110, n. 10, p. 724–732, 2002. ROMITI, N.; TONGIANI, R.; CERVELLI, F.; CHIELI, E. Effects of curcumin on P-glycoprotein in primary cultures of rat hepatocytes. Life Sciences. v. 62, p. 2349–2358, 1998. RUBY, A. J.; KUTTAN, G.; BABUB, K. D.; RAJASEKHARANB, K. N.; KUTTAN, R. Anti-tumor and antioxidant activity of natural curcuminoids. Cancer Letters. p. 79–83, 1995. RUTMAN, R. J.; CANTAROW, A.; PASCHKIS, K. E. The catabolism of uracil in vivo and in vitro. The Journal of Biological Chemistry. v. 210, n. 1, p. 321–329, 1954. SANTANA, R. O. Abordagens terapêuticas na mucosite oral experimental induzida por 5-fluorouracil: Papel dos extratos de Aloe barbadensis (babosa) e de Myracrodruon urundeuva (aroeira-do-sertão). 2006. 128p. Dissertação (Mestrado em Farmacologia), Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2006. SARGENT, D. J.; MARSONI, S.; MONGES, G.; THIBODEAU, S. N.; LABIANCA, R.; HAMILTON, S. R.; FRENCH, A. J.; KABAT, B.; FOSTER, N. R.; TORRI, V.; RIBIC, C.; GROTHEY, A.; MOORE, M.; ZANIBONI, A.; SEITZ, J. F.; SINICROPE, F.; GALLINGER, S. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. Journal of Clinical Oncology. v. 28, p. 3219–3226, 2010. SAVVA-BORDALO, J.; RAMALHO-CARVALHO, J.; PINHEIRO, M.; COSTA, V. L.; RODRIGUES, A.; DIAS, P. C.; VEIGA, I.; MACHADO, M.; TEIXEIRA, M. R.; HENRIQUE, H.; JERÓNIMO, C. Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients. BMC Cancer. v. 10, p. 420–427, 2010. SCARTEZZINI, P.; SPERONI, E. Review on some plants of Indian traditional medicine with antioxidant activity. Journal Ethnopharmacology. v. 71, p. 23–43, 2000. SCHLUTER, C.; DUCHROW, M.; WOHLENBERG, C.; BECKER, M. H.; KEY, G.; FLAD, H. D.; GERDES, J. The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. The Journal of Cell Biology. v. 123, p. 513–522, 1993. SCHOLZ, O. A.; WOLFF, A.; SCHUMACHER, A.; GIANNOLA, L. I.; CAMPISI, G.; CIACH, T.; VELTEN, T. Drug delivery from the oral cavity: focus on a novel mechatronic delivery device. Drug Discovery Today. v. 13, p. 247–253, 2008. SEIDLER, U.; LENZEN, H.; CINAR, A.; TESSEMA, T.; BLEICH, A.; RIEDERER, B. Molecular mechanisms of disturbed electrolyte transport in intestinal inflammation. Annals of the New York Academy of Sciences. v. 1072, p. 262–275, 2006. SHAIK, J.; ANKOLA, D. D.; BENIWAL, V.; SINGH, D.; KUMAR, M. N. Nanoparticle encapsulation improves oral biovailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. European Journal Pharmaceutical Sciences. v. 37, p. 223–230, 2009. SHIM, J. S.; KIM, J. H.; CHO, H. Y.; YUM, Y. N.; KIM, S. H.; PARK, H. J.; SHIM, B. S.; CHOI, S. H.; KWON, H. J. Irreversible inibition of CD13/aminopeptidase N by the antiangiogenic agent curcumin. Chemistry & Biology. v. 10, p. 695–704, 2003. SINGH, S.; DAS ROY, L.; GIRI, S. Curcumin Protects Metronidazole and X-ray Induced Cytotoxicity and Oxidative Stress in Male Germ Cells in Mice. Prague Medical Report. v. 114, n. 2, p. 92–102, 2013. SOARES, P. M.; LIMA-JUNIOR, R.C.; MOTA, J. M.; JUSTINO, P. F.; BRITO, G. A.; RIBEIRO, R. A.; CUNHA, F. Q.; SOUZA, M. H. Role of platelet-activating factor in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice. Cancer Chemotherapy and Pharmacology. v. 68, n. 3, p. 713–720, 2011. SOARES, P. M.; MOTA, J. M.; GOMES, A. S.; OLIVEIRA, R. B.; ASSREUY, A. M.; BRITO, G. A.; SANTOS, A. A.; RIBEIRO, R. A.; SOUZA, M. H. Gastrointestinal dysmotility in 5-fluorouracil-induced intestinal mucositis outlasts inflammatory process resolution. Cancer Chemotherapy and Pharmacology. v. 63, p. 91–98, 2008. SOARES, P. M.; MOTA, J. M.; SOUZA, E. P.; JUSTINO, P. F.; FRANCO, A. X.; CUNHA, F. Q.; RIBEIRO, R. A.; SOUZA, M. H. Inflammatory intestinal damage induced by 5-fluorouracil requires IL-4. Cytokine. v. 61, n. 1, p. 46–49, 2013. SOMPARN, P.; PHISALAPHONG, C.; NAKORNCHAI, S.; UNCHERN, S.; MORALES, N. P. Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives. Biological & Pharmaceutical Bulletin. v. 30, n. 1, p. 74–78, 2007. SON, T. G.; GONG, E. J.; BAE, M. J.; KIM, S. D.; HEO, K.; MOON, C.; YANG, K.; KIM, J. S. Protective effect of genistein on radiation-induced intestinal injury in tumor bearing mice. BMC Complementary and Alternative Medicine. v. 13, n. 1, 2013. SONIS, S. T. Mucositis: The impact, biology and therapeutic opportunities of oral mucositis. Oral Oncology. v. 45, n. 12, p. 1015–1020, 2009. SONIS, S. T. Pathobiology of oral mucositis: novel insights and opportunities. The Journal of Supportive Oncology. v. 5, p. 3–11, 2007. SONIS, S. T. Regimen-related gastrointestinal toxicities in cancer patients. Current Opinion in Supportive and Palliative Care. v. 4, n. 1, p. 26–30, 2010. SONIS, S. T.; ELTING, L. S.; KEEFE, D.; PETERSON, D. E.; SCHUBERT, M.; HAUER-JENSEN, M.; BEKELE, B. N.; RABER-DURLACHER, J.; DONNELLY, J. P.; RUBENSTEIN, E. B. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. v. 100, n. 9, p. 1995–2025, 2004. SONIS, S. T.; HADDAD, R.; POSNER, M.; WATKINS, B.; FEY, E.; MORGAN, T. V.; MOOKANAMPARAMBIL, L.; RAMONI, M. Gene expression changes in peripheral blood cells provide insight into the biological mechanisms associated with regimen-related toxicities in patients being treated for head and neck cancers. Oral Oncology. v. 43, p. 289–300, 2007. SONIS, S. T.; TRACEY, C.; SHKLAR, G.; JENSON, J.; FLORINE, D. An animal model for mucositis induced by cancer chemotherapy. Oral Surgery, Oral Medicine, Oral Pathology. v. 69, n. 4, p. 437-443, 1990. STEWART, B. W.; WILD, C. P.; World Cancer Report 2014. International Agency for Research on Cancer (IARC-OMS). Lyon, France, 2014. STRINGER, A. M.; GIBSON, R. J.; LOGAN, R. M.; BOWEN, J. M.; YEOH, A. S.; HAMILTON, J.; KEEFE, D. M. Gastrointestinal microflora and mucins may play a critical role in the development of 5-Fluorouracil-induced gastrointestinal mucositis. Experimental Biology and Medicine. v. 234, n. 4, p. 430–441. 2009. STROHMEIER, G. R.; REPPERT, S. M.; LENCER, W. I.; MADARA, J. L. The A2b adenosine receptor mediates cAMP responses to adenosine receptor agonists in human intestinal epithelia. The Journal of Biological Chemistry. v. 270, p. 2387–2394, 1995. STURM, A.; SUDERMANN, T.; SCHULTE, K. M.; GOEBELL, H.; DIGNASS, A. U. Modulation of intestinal epithelial wound healing in vitro and in vivo by lysophosphatidic acid. Gastroenterology. v. 117, p. 368–377, 1999. SUMANONT, Y.; MURAKAMI, Y.; TOHDA, M.; VAJRAGUPTA, O.; WATANABE, H.; MATSUMOTO, K. Prevention of kainic acid-induced changes in nitric oxide level and neuronal cell damage in the rat hippocampus by manganese complexes of curcumin and diacetylcurcumin. Life Sciences. v. 78, p. 1884–1891, 2006. SURYANARAYANA, P.; SARASWAT, M.; MRUDULA, T.; KRISHNA, T. P.; KRISHNASWAMY, K.; REDDY, G. B. Curcumin and turmeric delay streptozotocin-induced diabetic cataract in rats. Investigative Ophthalmology & Visual Science. v. 46, p. 2092–2099, 2005. TEITEN, M.; EIFES, S.; DICATO, M.; DIEDERICH, M. Curcumin - The Paradigm of a Multi-Target Natural Compound with Applications in Cancer Prevention and Treatment. Toxins. v. 2, p. 128–162, 2010. THORNBERRY, N. A. Caspases: key mediators of apoptosis. Chemistry & Biology. v. 5, n. 5, p. 97–103, 1998. TRAN, K. T.; GRIFFITH, L.; WELLS, A. Extracellular matrix signaling through growth factor receptors during wound healing. Wound Repair and Regeneration. v. 12, p. 262–268, 2004. van VLIET, M. J.; HARMSEN, H. J.; DE BONT, E. S.; TISSING, W. J. The role of intestinal microbiota in the development and severity of chemotherapy-induced mucositis. PLOS Pathogens. v. 6, n. 5, 2010. VARUM, F. O.; BASIT, A. W.; SOUSA, J.; VEIGA, F. Estudos de mucoadesão no trato gastrointestinal para o aumento da biodisponibilidade oral de fármacos. Revista Brasileira de Ciências Farmacêuticas. v. 44, n. 4, p. 535–548, 2008. VASCONCELOS, S. M. L.; GOULART, M. O. F.; MOURA, J. B. F.; MANFREDINI, V.; BENFATO, M. S.; KUBOTA, L. T. Espécies reativas de oxigênio e de nitrogênio, antioxidantes e marcadores de dano oxidativo em sangue humano: principais métodos analíticos para sua determinação. Química Nova. v. 30, n. 5, p. 1323–1338, 2007. VERBEEK, R.; van TOL, E. A.; van NOORT, J. M. Oral flavonoids delay recovery from experimental autoimmune encephalomyelitis in SJL mice. Biochemical Pharmacology. v. 70, p. 220–228, 2005. VILLANOVA, J. C. O.; OREFICE, R. L.; CUNHA, A. S. Aplicações farmacêuticas de polímeros. Polímeros. v. 20, n. 1, p. 51–64. 2010. von MEHREN, M.; WIDMER, N. Correlations between imatinib pharmacokinetics, pharmacodynamics, adherence, and clinical response in advanced metastatic gastrointestinal stromal tumor (GIST): an emerging role for drug blood level testing? Cancer Treatment Reviews. v. 37, p. 291–299, 2011. WAGNER, J. G.; ROTH, R. A. Neutrophil migration mechanisms, with an emphasis on the pulmonary vasculature. Pharmacological Reviews. v. 52, n. 1, p. 349–374, 2000. WANG, S.; ZHAO, Z.; XIE, T.; ZENG, Z.; ZHAN, X.; WANG, A. Recent advances in the study of elemene on cancer. Journal of Medicinal Plants Research. v. 6, n. 46, p. 5720–5729, 2012. WERLE, M.; BERNKOP-SCHNÜRCH, A. Thiolated chitosans: useful excipients for oral drug delivery. Journal of Pharmacy and Pharmacology. v. 60, n. 3, p. 273–281, 2008. WILSON, A. J.; GIBSON, P. R. Epithelial migration in the colon: filling in the gaps. Clinical Science. v. 93, p. 97–108, 1997. WIWANITKIT, V. Effect of interleukin-2 and tumor necrosis factor-alpha on osteopontin: molecular function and biological process. Pediatrics International. v. 50, n. 2, p. 213–215, 2008. WONG, V. C.; MORSE, J. L.; ZHITKOVICH, A. p53 activation by Ni(II) is a HIF-1α independent response causing caspases 9/3-mediated apoptosis in human lung cells. Toxicology and Applied Pharmacology. 2013. WORLD HEALTH ORGANIZATION – WHO. June, 2011. The top 10 causes of death. Disponível em: <http://who.int/mediacentre/factsheets/fs310/en/>. Acesso em: 17 mar. 2013. WU, J.; LI, Q.; WANG, X.; YU, S.; LI, L.; WU, X.; CHEN, Y.; ZHAO, J.; ZHAO, Y. Neuroprotection by curcumin in ischemic brain injury involves the akt/nrf2 pathway. PLoS One. v. 8, n. 3, 2013. XU, Y.; KU, B. S.; YAO, H. Y.; LIN, Y. H.; MA, X.; ZHANG, Y. H.; LI, X. J. Antidepressant effects of curcumin in the forced swin test and olfactory bulbectomy models of depression in rats. Pharmacology Biochemistry. v. 82, p. 200–206, 2005. YANG, C. L.; LIU, Y. Y.; MA Y. G.; XUE, Y. X.; LIU, D. G.; REN, Y.; LIU, X. B.; LI, Y; LI, Z. Curcumin blocks small cell lung cancer cells migration, invasion, angiogenesis, cell cycle and neoplasia through Janus kinase-STAT3 signalling pathway. PLoS One. v.7, n. 5, 2012. YANG, J.; RAMNATH, N.; MOYSICH, K. B.; ASCH, H. L.; SWEDE, H.; ALRAWI, S. J.; HUBERMAN, J.; GERADTS, J.; BROOKS, J. S.; TAN, D. Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer. BMC Cancer. v. 6, p. 203–213, 2006. YANG, K. Y.; LIN, L. C.; TSENG, T. Y.; WANG, S. C.; TSAI, T. H. Oral bioavailability of curcumin in rat and the herbal analysis from Curcuma longa by LC-MS/MS. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. v. 853, p. 183–189, 2007. YAO, Q.; YE, X.; WANG, L.; GU, J.; FU, T.; WANG, Y.; LAI, Y.; WANG, Y.; WANG, X.; JIN, H.; GUO, Y. Protective effect of Curcumin on chemotherapy-induced intestinal dysfunction. International Journal of Clinical and Experimental Pathology. v. 6, n. 11, p. 2342–2349, 2013. YEOH, A. S.; GIBSON, R. J.; YEOH, E. E.; BOWEN, J. M.; STRINGER, A. M.; GIAM, K. A.; KEEFE, D. M. A novel animal model to investigate fractionated radiotherapy-induced alimentary mucositis: the role of apoptosis, p53, nuclear factor-kappaB, COX-1, and COX-2. Molecular Cancer Therapeutics. v. 6, n. 8, p. 2319–2327, 2007. YODKEEREE, S.; GARBISA, S.; LIMTRAKUL, P. Tetrahydrocurcumin inhibits HT1080 cell migration and invasion via downregulation of MMPs and uPA. Acta Pharmacologica Sinica. v. 29, n. 7, p. 853–860, 2008. YOUSSEF, K. M.; EL-SHERBENY, M. A.; EL-SHAFIE, F. S.; FARAG, H. A.; AL-DEEB, O. A.; AWADALLA, S. A. Synthesis of curcumin analogues as potencial antioxidant, cancer chemopreventive agents. Arch Pharmazine. v. 337, p. 42–54, 2004. ZHANG, B.; ZHANG, X.; TANG, B.; ZHENG, P.; ZHANG, Y. Investigation of elemene-induced reversal of tamoxifen resistance in MCF-7 cells through estrogen receptor α (ERα) re-expression. Breast Cancer Research and Treatment. v. 136, n. 2, p. 399–406, 2012. ZHANG, J.; OWEN, C. R.; SANDERS, M. A.; TURNER, J. R.; BASSON, M. D. The mutagenic effects of cyclic mechanical strain on intestinal epithelial monolayer wound closure are matrix dependent. Gastroenterology. v. 131, n. 4, p. 1179–1189, 2006. ZHU, J.; BULTYNCK, G.; LUYTEN, T.; PARYS, J. B.; CREEMERS, J. W.; VAN DE VEN, W. J.; VERMORKEN, A. J. Curcumin affects proprotein convertase activity: elucidation of the molecular and subcellular mechanism. Biochimica et Biophysica Acta. v. 1833, n. 8, p. 1924–1935, 2013. ZÖRNIG, M.; HUEBER, A.; BAUM, W.; EVAN, G. Apoptosis regulators and their role in tumorigenesis. Biochimica et Biophysica Acta. v. 1551, n. 2, 1–37, 2001. ZUURBIER, K. W.; VAN DEN BERG, J. D.; VAN GELDER, B. F.; MUIJSERS, A. O. Human hemi-myeloperoxidase. Initial chlorinating activity at neutral pH, compound II and III formation, and stability towards hypochlorous acid and high temperature. European Journal of Biochemistry, v. 205, n. 2, p. 737–742, 1992. | por |
| dc.rights | Acesso Aberto | por |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject | Mucosite intestinal | por |
| dc.subject | 5-fluorouracil | por |
| dc.subject | Curcuma longa L. | por |
| dc.subject | Formulação mucoadesiva | por |
| dc.subject | Intestinal mucositis | eng |
| dc.subject | Mucoadhesive formulation | eng |
| dc.subject.cnpq | CIENCIAS DA SAUDE::FARMACIA | por |
| dc.thumbnail.url | http://repositorio.bc.ufg.br/tede/retrieve/8209/Santos%20Filho%2c%20Edvande-2014-disserta%c3%a7%c3%a3o.pdf.jpg | * |
| dc.title | Efeitos da formulação mucoadesiva com extrato de Curcuma longa L. em animais portadores de mucosite intestinal induzida por 5-fluorouracil | por |
| dc.type | Dissertação | por |
Arquivos
Pacote Original
1 - 1 de 1
Carregando...
- Nome:
- Santos Filho, Edvande-2014-dissertação.pdf
- Tamanho:
- 3.3 MB
- Formato:
- Adobe Portable Document Format
- Descrição:
Licença do Pacote
1 - 1 de 1
Nenhuma Miniatura disponível
- Nome:
- license.txt
- Tamanho:
- 2.11 KB
- Formato:
- Item-specific license agreed upon to submission
- Descrição: