Efeitos da capsaicina na etapa de promoção/progressão da carcinogênese química de colón em ratos
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Data
2018-07-31
Autores
Tablas, Mariana Baptista [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A capsaicina (8-metil-N-vanilil-trans-6-nonamida) é uma substância alcaloide de natureza lipofílica, responsável pela pungência de pimentas e pimentões. Apresenta propriedades anti-inflamatória, antimicrobiana e antioxidante bem descritas na literatura científica. Assim, este projeto teve como objetivo investigar se a capsaicina apresenta efeito quimioprotetor quando administrada na etapa de promoção/progressão da carcinogênese de cólon induzida pela 1,2-dimetilhidrazina (DMH). Ratos Wistar machos foram alocados em seis grupos experimentais com 10 a 15 animais cada. Os animais dos grupos 1-3 receberam quatro injeções subcutâneas (s.c) do carcinógeno DMH (40mg/kg, duas doses/semana) e os animais do grupo 4-6 receberam quatro injeções s.c de solução de EDTA .Os grupos 2 e 4 receberam por gavagem 5mg/kg p.c e os grupos 3 e 5 receberam 50mg/kg p.c de capsaicina diluída em óleo de milho até o final da 24ª semana do experimento. Após a eutanásia dos animais, os cólons distal, medial e proximal foram corados com azul de metileno a 2% para detecção de focos de criptas aberrantes (FCA). Após a análise de FCAs, os cólons foram processados para análise histológica e classificação de tumores. As amostras congeladas foram utilizadas para análise de expressão de gênica pela técnica Taqman® Low Density Array (TLDA). Os níveis séricos de ALT (p=0,346) e creatinina (p=0,854) foram semelhantes entre os grupos, mostrando que as doses de capsaicina utilizadas não apresentaram ação citotóxica para o fígado e rins. Na análise estereoscópica de FCA, observou-se diminuição significativa de lesões no cólon do grupo que recebeu a maior dose de capsaicina (G3) em relação ao grupo G1 (p< 0,05). Redução nos níveis de proliferação celular nos tumores colônicos (p=0,0002), nas criptas colônicas normais (p= 0,0071) e na incidência de adenocarcinoma tubulares foram menores no grupo G3 em relação ao grupo G1. Na análise de expressão gênica dos tumores foi observada menor expressão dos genes Cebpd e Faslg responsáveis pela diferenciação celular, crescimento tumoral, invasividade e proliferação celular no grupo G3 em relação ao G1. Concluímos que este estudo apontam para efeitos supressores da capsaicina no desenvolvimento de lesões colônicas pré e neoplásicas.
Capsaicin (8-Methyl-N-vanillyl-(trans)-6-nonenamide) is a lipophilic alkaloid, responsible for the pungency in pepper. Its antiinflamatory, antimicrobial and antioxidant properties are well described in the scientific literature. Thus, the objective of this study was to investigate whether capsaicin exerts a chemoprotective effect when administered during 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis promotion/progression in rates. Male Wistar rats were allocated into six groups of 10-15 animals each. Groups 1-3 received 4 subcutaneous injections of DMH (40 mg/kg bw, 2 doses/week), while groups 4-6 received EDTA solution (DMH vehicle, 2 doses/week), followed by intragastric 5mg/kg bw capsaicin diluted in corn oil (G2, G4) or 50mg/kg bw (G3, G5) for 24 weeks (3 doses/week). After sacrifice, blood samples were drawn by heart puncture for the assessment of serum alanine aminotransferase (ALT) and creatinine levels, and the colon was removed. A segment of distal colon and colon tumor samples were frozen in liquid nitrogen at -80ºC. Distal, medial and proximal colon samples were stained with 2% methylene blue for the detection of aberrant crypt foci (ACF).After ACF analysis, colon tumors were processed for histological analysis and tumor classification. The frozen samples were used for the analysis of gene expression by Taqman® Low Density Array (TLDA). Serum ALT (p=0.346) and creatinine (p=0.854) levels were similar among groups, indicating that the capsaicin doses used had no cytotoxic effect on the liver and kidneys. ACF analysis showed that the number of colon lesions was significantly lower in the group given the higher capsaicin dose (G3) than in G1 (p<0,05). Cell proliferation in colon tumors (p=0.0002), the number of normal colonic crypts (p= 0.0071), and the incidence of tubular adenocarcinoma were lower in G3 than in G1. Gene expression of Cebpd and Faslg genes; responsible for cell differentiation, tumor growth, invasiveness, and cell proliferation; was decreased in tumor from G3. We conclude that this study points to the suppressive effects of capsaicin in the development of pre and neoplastic colonic lesions.
Capsaicin (8-Methyl-N-vanillyl-(trans)-6-nonenamide) is a lipophilic alkaloid, responsible for the pungency in pepper. Its antiinflamatory, antimicrobial and antioxidant properties are well described in the scientific literature. Thus, the objective of this study was to investigate whether capsaicin exerts a chemoprotective effect when administered during 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis promotion/progression in rates. Male Wistar rats were allocated into six groups of 10-15 animals each. Groups 1-3 received 4 subcutaneous injections of DMH (40 mg/kg bw, 2 doses/week), while groups 4-6 received EDTA solution (DMH vehicle, 2 doses/week), followed by intragastric 5mg/kg bw capsaicin diluted in corn oil (G2, G4) or 50mg/kg bw (G3, G5) for 24 weeks (3 doses/week). After sacrifice, blood samples were drawn by heart puncture for the assessment of serum alanine aminotransferase (ALT) and creatinine levels, and the colon was removed. A segment of distal colon and colon tumor samples were frozen in liquid nitrogen at -80ºC. Distal, medial and proximal colon samples were stained with 2% methylene blue for the detection of aberrant crypt foci (ACF).After ACF analysis, colon tumors were processed for histological analysis and tumor classification. The frozen samples were used for the analysis of gene expression by Taqman® Low Density Array (TLDA). Serum ALT (p=0.346) and creatinine (p=0.854) levels were similar among groups, indicating that the capsaicin doses used had no cytotoxic effect on the liver and kidneys. ACF analysis showed that the number of colon lesions was significantly lower in the group given the higher capsaicin dose (G3) than in G1 (p<0,05). Cell proliferation in colon tumors (p=0.0002), the number of normal colonic crypts (p= 0.0071), and the incidence of tubular adenocarcinoma were lower in G3 than in G1. Gene expression of Cebpd and Faslg genes; responsible for cell differentiation, tumor growth, invasiveness, and cell proliferation; was decreased in tumor from G3. We conclude that this study points to the suppressive effects of capsaicin in the development of pre and neoplastic colonic lesions.
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Palavras-chave
Capsaicina, Carcinogênese de cólon, Quimioprevenção, Capsaicin, Colon carcinogenesis, Chemoprevention