Caquexia muscular associada ao desenvolvimento de cancro da bexiga em ratos machos Wistar
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2016-07-08
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A caquexia muscular associada ao cancro é uma condição paraneoplásica preocupante.
Caquexia, etimologicamente significa “mau estado”, é uma síndrome complexa e multifatorial, que se caracteriza pela perda de tecido adiposo e posterior consumo do músculo-esquelético. Sendo o cancro, só por si, uma doença muito grave, quando associado à caquexia a situação complica-se porque a piorar o estado geral dos doentes. Apesar dos mecanismos subjacentes à caquexia ainda não estarem completamente esclarecidos, julga-se que esta síndrome paraneoplásica está associada a alterações metabólicas, imunológicas e inflamatórias. No presente trabalho, pretendemos avaliar as alterações de parâmetros bioquímicos no soro potencialmente sugestivos de caquexia e relacionar com alterações de massa corporal, massa muscular e caraterísticas histológicas do tumor, utilizando um modelo de cancerização urotelial pela administração oral da N-butil-N-(4-hidroxibutil) nitrosamina (BBN), a ratos machos da estirpe Wistar. Neste sentido, constituíram-se dois grupos experimentais: grupo BBN: (animais expostos à BBN durante 20 semanas) e grupo controlo. No final do protocolo animal, os animais foram anestesiados e procedeu-se à sua necropsia. Nas amostras de soro obtidas, a partir do sangue colhido no momento do sacrifício, foram determinados os seguintes parâmetros bioquímicos: alanina aminotransferase, aspartato aminotransferase, creatina cinase, fosfatase alcalina, albumina, proteína total, colesterol, triglicerídeos e glucose. Paralelamente, procedeu-se à avaliação das lesões uroteliais em seções de tumor coradas com hematoxilina-eosina. No grupo BBN, 50% dos animais apresentaram uma perda de massa corporal superior a 5%. Destes, 50% apresentaram perda de massa do músculo gastrocnemius superior a 5%. Relativamente à percentagem das lesões uroteliais, no grupo BBN identificaram-se 83,3% de hiperplasia simples, 50% de hiperplasia nodular, 8,3% de hiperplasia papilar, 50% de papiloma, 41,7% de tumor papilar de baixo potencial maligno, 91,7% de carcinoma papilar de baixo grau, 66,7% de carcinoma papilar de alto grau, 8,3% de carcinoma invasor e 50% de metaplasia epidermoide com queratinização. No grupo controlo não se identificou quaisquer alterações histológicas. O estado de caquexia dos animais expostos à BBN foi corroborado pela diminuição dos níveis séricos da albumina, da proteína total, da atividade da CK, da ALT, da ALP e da AST. Os resultados sugerem que os animais com tumores da bexiga são suscetíveis ao desenvolvimento de caquexia devida à perda de massa muscular o que, nos estádios iniciais se traduz bioquimicamente na alteração de parâmetros séricos.
Cancer-related muscle wasting associated is a paraneoplastic condition that worsens disease prognosis and clinical outcomes. Cachexia, etymologically means "bad state", is a complex and multifactorial syndrome characterized by the loss of fat tissue and skeletal muscle. Although the mechanisms underlying cachexia still not completely understood, it is believed that this cancer cachexia is associated with metabolic, immunological and inflammatory alterations. In this work, we intend to evaluate the changes in serum biochemical parameters potentially suggestive of cachexia and correlate with changes in body weight, muscle mass and histological features of the tumor, using a model of urothelial cancerization by oral administration of N - butyl- N - (4-hydroxybutyl) nitrosamine (BBN) in male rats of the Wistar strain. In this study, two experimental groups were formed: BBN (animals exposed to BBN for 20 weeks) and control groups. At the end of the protocol, the animals were anesthetized and proceeded to their necropsy. Serum samples obtained from the blood collected at the time of sacrifice were uded for the assay of the following biochemical parameters: alanine aminotransferase, aspartate aminotransferase, creatine kinase, alkaline phosphatase, albumin, total protein, cholesterol, triglycerides and glucose. In parallel, we proceeded to the evaluation of urothelial lesions in tumor sections stained with hematoxylin-eosin. In the BBN group, 50% of the animals showed a loss of body mass over 5%. Of these, 50% presented more than 5% of gastrocnemius mass loss. Regarding the percentage of urothelial lesions in the BBN group we identified 83.3 % of simple hyperplasia, 50 % of nodular hyperplasia, 8.3% of papillary hyperplasia, papilloma 50 %, 41.7 % of papillary tumor of low potential malignant, 91.7 % of low-grade papillary carcinoma, 66.7 % of high-grade papillary carcinoma, carcinoma of 8.3% and 50 % of squamous metaplasia with keratinization . In the control group, no histological changes were identified. The decrease in serum albumin, total protein and in the activity of CK, ALT, ALP and AST observed in BBN animals seem to corroborate cachexia. The results suggest that animals with bladder tumors are susceptible to the development of cancer cachexia reflected in changes of biochemical serum parameters in disease initial stages.
Cancer-related muscle wasting associated is a paraneoplastic condition that worsens disease prognosis and clinical outcomes. Cachexia, etymologically means "bad state", is a complex and multifactorial syndrome characterized by the loss of fat tissue and skeletal muscle. Although the mechanisms underlying cachexia still not completely understood, it is believed that this cancer cachexia is associated with metabolic, immunological and inflammatory alterations. In this work, we intend to evaluate the changes in serum biochemical parameters potentially suggestive of cachexia and correlate with changes in body weight, muscle mass and histological features of the tumor, using a model of urothelial cancerization by oral administration of N - butyl- N - (4-hydroxybutyl) nitrosamine (BBN) in male rats of the Wistar strain. In this study, two experimental groups were formed: BBN (animals exposed to BBN for 20 weeks) and control groups. At the end of the protocol, the animals were anesthetized and proceeded to their necropsy. Serum samples obtained from the blood collected at the time of sacrifice were uded for the assay of the following biochemical parameters: alanine aminotransferase, aspartate aminotransferase, creatine kinase, alkaline phosphatase, albumin, total protein, cholesterol, triglycerides and glucose. In parallel, we proceeded to the evaluation of urothelial lesions in tumor sections stained with hematoxylin-eosin. In the BBN group, 50% of the animals showed a loss of body mass over 5%. Of these, 50% presented more than 5% of gastrocnemius mass loss. Regarding the percentage of urothelial lesions in the BBN group we identified 83.3 % of simple hyperplasia, 50 % of nodular hyperplasia, 8.3% of papillary hyperplasia, papilloma 50 %, 41.7 % of papillary tumor of low potential malignant, 91.7 % of low-grade papillary carcinoma, 66.7 % of high-grade papillary carcinoma, carcinoma of 8.3% and 50 % of squamous metaplasia with keratinization . In the control group, no histological changes were identified. The decrease in serum albumin, total protein and in the activity of CK, ALT, ALP and AST observed in BBN animals seem to corroborate cachexia. The results suggest that animals with bladder tumors are susceptible to the development of cancer cachexia reflected in changes of biochemical serum parameters in disease initial stages.
Descrição
Dissertação de Mestrado em Biologia Clínica e Laboratorial
Palavras-chave
Carcinogénese (química) , Músculo esquelético , Lesões uroteliais , Massa corporal