Efeito do canabidiol, um componente da cannabis sativa, na mucosite oral induzida em camundongos sob quimioterapia com 5-fluorouracil : avalia??o cl?nica, histol?gica, hematol?gica e bioqu?mica

• Main Author: Guerra, Leticia de Freitas Cuba
• Other Authors: Figueiredo, Maria Ant?nia Zancanaro de
• Format: Others
• Language: Portuguese
• Published: Pontif?cia Universidade Cat?lica do Rio Grande do Sul 2018
• Subjects: Estomatologia; Quimioterapia; Mucosite Oral; Antioxidantes; Canabidiol; Stomatology; Chemotherapy; Oral Mucositis; Antioxidants; Cannabidiol; CIENCIAS DA SAUDE::ODONTOLOGIA
• Online Access: http://tede2.pucrs.br/tede2/handle/tede/8376

Submitted by PPG Odontologia ([e-mail]) on 2018-12-11T12:24:17Z No. of bitstreams: 1 LETICIA_DE_FREITAS_CUBA_GUERRA_TESE.pdf: 2732307 bytes, checksum: bc2400c7b447bde4664cb97c02124ea6 (MD5) === Approved for entry into archive by Sheila Dias ([e-mail]) on 2018-12-13T10:59:32Z (GMT) No. of bitstreams: 1 LETICIA_DE_FREITAS_CUBA_GUERRA_TESE.pdf: 2732307 bytes, checksum: bc2400c7b447bde4664cb97c02124ea6 (MD5) === Made available in DSpace on 2018-12-13T11:08:39Z (GMT). No. of bitstreams: 1 LETICIA_DE_FREITAS_CUBA_GUERRA_TESE.pdf: 2732307 bytes, checksum: bc2400c7b447bde4664cb97c02124ea6 (MD5) Previous issue date: 2018-10-19 === Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES === Malignant neoplasms are a public health problem worldwide. The global estimate shows that in 2012, there were 14.1 million new cases of cancer and 8.2 million deaths. The epidemiology of cancer shows the importance of advancement in research in the area, from strategies of early diagnosis to containment of the damages associated with its occurrence and therapies used. Currently, the main treatment modalities include surgery, radiotherapy (RT) and chemotherapy (CT). CT is widely used in the treatment of solid and hematological malignancies, where its aim is to destroy the tumor cells. However, it is not selective and also affects healthy cells of rapid renewal, such as those of the oral mucosa. As a consequence of damage to normal cells, this therapy accounts for substantial deleterious effects, such as oral mucositis (OM). This condition is characterized by the presence of painful ulcerations that can progress to such severe conditions, where the course of cancer treatment is compromised. Associated with the etiology of OM is oxidative stress (OS) generated by CT, which can induce the production of reactive oxygen species (ROS), responsible for cell damage and the initiation tissue lesions. Cannabidiol (CBD) is the main non-psychotropic component of Cannabis sativa and has potent antiinflammatory, antioxidant and analgesic effects. This thesis consists of 2 scientific papers. The first is a literature review, whose objective was to evaluate the different mechanisms of action of CBD, which may be involved in the prevention and management of OM, suggesting the promising property of this drug. The second one deals with an experimental study conducted in an animal model, with the objective of evaluating the clinical, histological, hematological and oxidative stress effects of the intraperitoneal administration of CBD, at doses of 3, 10 and 30 mg/kg for 4 and 7 days, in the repair of chemo-induced OM on the tongue ventrum of 90 CF-1 mice. CBD treatment decreased the OM clinic scores at both experimental times (p<0.005) and reduced the intensity of the inflammatory response, but not statistically significant. With regard to erythrocyte, leukocyte and platelet counts and antioxidant enzyme activity, CAT and GSH, the groups treated with CBD showed better results. Thus, we concluded that CBD is able to regulate the inflammatory process of OM, and may represent a promising alternative in the management of this condition. === As neoplasias malignas representam um problema de sa?de p?blica mundial. As estimativas mostram que, em 2012, ocorreram 14,1 milh?es de casos novos de c?ncer e 8,2 milh?es de ?bitos. A epidemiologia do c?ncer denota a import?ncia do avan?o em pesquisas na ?rea, desde estrat?gias de diagn?stico precoce ? conten??o dos danos associados a sua ocorr?ncia e terap?utica empregada. Atualmente, as principais modalidades de tratamento contemplam a cirurgia, a radioterapia (RT) e a quimioterapia (QT). A QT ? amplamente empregada no tratamento de neoplasias malignas s?lidas e hematol?gicas, uma vez que age destruindo as c?lulas tumorais. No entanto, n?o ? seletiva, atingindo tamb?m c?lulas saud?veis de r?pida renova??o como as da mucosa oral. Em consequ?ncia ao dano ?s c?lulas normais, esta terapia gera efeitos delet?rios importantes como, por exemplo, a mucosite oral (MO). Esta condi??o caracteriza-se pela presen?a de ulcera??es dolorosas que podem evoluir para quadros t?o graves que comprometam o curso do tratamento oncol?gico. Associada a etiologia da MO est? o estresse oxidativo (EO) gerado pela QT, que seria capaz de induzir a produ??o de esp?cies reativas de oxig?nio (ROS) respons?veis pelo dano celular e inicia??o das les?es. O canabidiol (CBD) ? o principal componente n?o-psicotr?pico da Cannabis sativa e desempenha potentes efeitos antiinflamat?rios, antioxidantes e analg?sicos. A presente tese est? estruturada na forma de 2 artigos cient?ficos. O primeiro consiste em uma revis?o de literatura, cujo objetivo foi avaliar os diferentes mecanismos de a??o do CBD que possam estar envolvidos na preven??o e manejo da MO, sugerindo o car?ter promissor desta droga. O segundo trata de um estudo experimental desenvolvido em modelo animal, com objetivo de avaliar a resposta cl?nica, histol?gica, hematol?gica e estresse oxidativo da administra??o intraperitoneal do CBD, nas doses de 3 mg/kg, 10 mg/kg e 30 mg/kg por 4 e 7 dias, no reparo da MO quimioinduzida no ventre lingual de 90 camundongos CF-1. O tratamento com CBD foi capaz de diminuir os escores cl?nicos da MO em ambos os tempos experimentais (p < 0,005) e reduziu a intensidade da resposta inflamat?ria, por?m sem signific?ncia estat?stica. Na contagem de eritr?citos, leuc?citos, plaquetas e atividade das enzimas antioxidantes CAT e GSH, observou-se melhores resultados nos grupos tratados com CBD. Dessa forma, concluiu-se que o CBD ? capaz de regular o processo inflamat?rio da MO, podendo representar uma alternativa promissora no manejo dessa condi??o.