Indução química e hormonal de cancro da próstata em ratos Wistar Unilever e a sua correlação com os efeitos do exercício físico – Potencial terapia auxiliar
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2018-02-09
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O cancro da próstata (CP) assume a quarta posição ao nível de incidência global de neoplasias pela World Health Organization (WHO). Vários modelos animais foram desenvolvidos para estudar o CP. Está disponível literatura científica sobre a aplicação do exercício físico como uma terapia auxiliar à doença, mas os mecanismos biológicos subjacentes ainda não foram descritos. A ultrassonografia é uma componente da imagiologia importante para monitorizar diversas doenças, nomeadamente o CP. Assim, o objetivo deste trabalho foi estudar e monitorizar por ultrassonografia o protocolo de indução de CP em animais de laboratório e compreender a influência do exercício na sua evolução. Para se alcançarem os objetivos propostos recorremos a um modelo animal de indução de CP, com ratos Wistar, através da administração sequencial de flutamida (fármaco anti-androgénio), propionato de testosterona, N-metil-N-nitrosureia (MNU) e a colocação de implantes de testosterona cristalina. Usaram-se 41 ratos de sexo masculino Wistar Unilever, distribuídos aleatoriamente por quatro grupos experimentais: grupo I, composto por 10 animais de controlo sedentários; grupo II, por 10 animais controlo exercitados; grupo III, por 10 animais induzidos ao CP sedentários; e um grupo IV, por 11 animais com CP induzido e exercitados. Os grupos II e IV foram submetidos a um plano de exercício crónico de corrida em tapete rolante. A massa corporal dos animais foi determinada e os consumos de água e comida registados periodicamente. A próstata de cada animal foi monitorizada nas semanas 12, 15, 21, 32 de vida, usando o modo B de ultrassonografia e na semana 35, pela técnica descrita e pelo modo de Contraste. Na semana 35 de vida, os animais foram sacrificados e realizou-se uma necrópsia completa, sendo recolhidos todos os órgãos e registadas as suas massas. Na semana 35, o valor médio da massa corporal dos animais exercitados (II e IV) foi inferior (p<0,05) aos animais sedentários (I e III). O protocolo de indução de CP não promoveu diferenças significativas na massa corporal (p>0,05). Os animais induzidos (III e IV) apresentaram uma dimensão prostática superior e uma ecogenicidade inferior (p<0,05) em comparação com os animais saudáveis (I e II). Não se registou qualquer indício de neovascularização. A massa relativa da próstata, da vesícula seminal e da glândula bulbouretral foi estatisticamente superior (p<0,05) no grupo III e IV. Não se registou qualquer efeito do exercício físico na glândula, através dos resultados obtidos. Conclui-se que a manipulação hormonal e a administração da MNU causa repercussões significativas nas dimensões da próstata (provocada pela proliferação de células no tecido) e nos valores de massa relativa dos órgãos reprodutores. Os dados sugerem que este protocolo de indução apresenta um período de latência elevado, presumindo a inexistência de lesões neoplásicas para o intervalo a que foi aplicado. Não foi possível aprofundar o efeito do exercício sobre o CP devido à ausência da análise histológica. Este estudo evidencia a importância da ultrassonografia na caraterização e monitorização da próstata num protocolo animal de indução de CP.
Prostate cancer (PC) is ranked fourth in the overall incidence of neoplasms by the World Health Organization (WHO). Several animal models were developed to study PC. Scientific literature on the application of physical exercise as an adjunctive therapy to the disease is available, but the underlying biological mechanisms have not yet been described. Ultrasonography is an important component of imaging to monitor various diseases, namely PC. Thus, the objective of this work was to study and monitor by ultrasonography the protocol of PC induction in laboratory animals and to understand the influence of exercise on its evolution. To achieve the proposed objectives, we used an animal model of PC induction, with Wistar rats, through the sequential administration of flutamide (anti-androgen drug), testosterone propionate, N-methyl-N-nitrosourea (MNU) and the placement of testosterone crystalline implants. Forty-one males Wistar Unilever rats randomly assigned to four experimental groups were used: group I, composed of 10 control animals; group II, composed of 10 control exercised; group III, composed of 10 induced to the PC sedentary; and one group IV, composed of 11 PC induced and exercised. Groups II and IV underwent a chronic treadmill exercise plan. The body mass of the animals was determined, and the water and food consumption were recorded periodically. The prostate of each animal was monitored at 12, 15, 21, 32 weeks of life, in B mode of ultrasonography and at week 35, using the described technique and by the Contrast mode. At week 35 of life, the animals were sacrificed and a complete necropsy was performed, all organs were collected and their mass recorded. At week 35, the mean body mass of the exercised animals (II and IV) was lower (p<0.05) than the sedentary animals (I and III). The PC induction protocol did not promote significant differences in body mass (p>0.05). Induced animals (III and IV) had a higher prostatic dimension and lower echogenicity (p<0.05) when compared with healthy animals (I and II). There was no evidence of neovascularization. The relative mass of the prostate, seminal vesicle and bulbourethral gland was statistically superior (p<0.05) in groups III and IV. There was no effect of physical exercise on the gland, through the results obtained. It is concluded that hormonal manipulation and MNU administration cause significant repercussions on the size of the prostate (caused by the proliferation of cells in the tissue) and in the relative mass values of the reproductive organs. It is suggested that this induction protocol presents a period of high latency, presuming the absence of neoplastic lesions for the interval to which it was applied. It was not possible to deepen the effect of exercise on PC due to absence of histological analysis. This study evidences the importance of ultrasonography in the characterisation and monitoring of the prostate in an animal PC induction protocol.
Prostate cancer (PC) is ranked fourth in the overall incidence of neoplasms by the World Health Organization (WHO). Several animal models were developed to study PC. Scientific literature on the application of physical exercise as an adjunctive therapy to the disease is available, but the underlying biological mechanisms have not yet been described. Ultrasonography is an important component of imaging to monitor various diseases, namely PC. Thus, the objective of this work was to study and monitor by ultrasonography the protocol of PC induction in laboratory animals and to understand the influence of exercise on its evolution. To achieve the proposed objectives, we used an animal model of PC induction, with Wistar rats, through the sequential administration of flutamide (anti-androgen drug), testosterone propionate, N-methyl-N-nitrosourea (MNU) and the placement of testosterone crystalline implants. Forty-one males Wistar Unilever rats randomly assigned to four experimental groups were used: group I, composed of 10 control animals; group II, composed of 10 control exercised; group III, composed of 10 induced to the PC sedentary; and one group IV, composed of 11 PC induced and exercised. Groups II and IV underwent a chronic treadmill exercise plan. The body mass of the animals was determined, and the water and food consumption were recorded periodically. The prostate of each animal was monitored at 12, 15, 21, 32 weeks of life, in B mode of ultrasonography and at week 35, using the described technique and by the Contrast mode. At week 35 of life, the animals were sacrificed and a complete necropsy was performed, all organs were collected and their mass recorded. At week 35, the mean body mass of the exercised animals (II and IV) was lower (p<0.05) than the sedentary animals (I and III). The PC induction protocol did not promote significant differences in body mass (p>0.05). Induced animals (III and IV) had a higher prostatic dimension and lower echogenicity (p<0.05) when compared with healthy animals (I and II). There was no evidence of neovascularization. The relative mass of the prostate, seminal vesicle and bulbourethral gland was statistically superior (p<0.05) in groups III and IV. There was no effect of physical exercise on the gland, through the results obtained. It is concluded that hormonal manipulation and MNU administration cause significant repercussions on the size of the prostate (caused by the proliferation of cells in the tissue) and in the relative mass values of the reproductive organs. It is suggested that this induction protocol presents a period of high latency, presuming the absence of neoplastic lesions for the interval to which it was applied. It was not possible to deepen the effect of exercise on PC due to absence of histological analysis. This study evidences the importance of ultrasonography in the characterisation and monitoring of the prostate in an animal PC induction protocol.
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Wistar , próstata , N-metil-N-nitrosureia (MNU) , testosterona , exercício , ultrassonografia