Lesões pré-neoplásicas, perfil lipídico, marcadores inflamatórios e aspecto histológico intestinal de ratos Wistar alimentados com dietas à base de diferentes óleos
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2010-02-18
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Universidade Federal de Viçosa
Resumo
A ação de óleos e gorduras na nutrição humana tem sido amplamente pesquisada e discutida nas últimas décadas. Atenção tem sido dada à qualidade nutricional destes óleos, sendo importante a quantidade e composição dos ácidos graxos. Os ácidos graxos essenciais têm grande importância por seus papéis farmacológicos e como mediadores de reações inflamatórias, diretamente relacionadas à resistência imunológica, distúrbios metabólicos, processos trombóticos e doenças neoplásicas. Estudos experimentais sustentam a hipótese que os ácidos graxos da série ω6 contribuem para o desenvolvimento a progressão de lesões neoplásicas enquanto que os ácidos graxos da série ω3 possuem uma ação protetora. O presente estudo teve como objetivo avaliar os efeitos da adição à dieta de diferentes óleos (soja, oliva, peixe, linhaça) na prevenção de lesões préneoplásicas no cólon de ratos Wistar. Avaliou-se ainda, o seu efeito no perfil lipídico, marcadores inflamatórios, migração de células inflamatórias e análise histológica da mucosa intestinal dos animais. Foram realizados dois experimentos. No primeiro, um estudo exploratório foi realizado com ratos Wistar adultos alimentados com dietas normolipídicas AIN-93M (4g/100g dieta). Os animais foram divididos em quatro grupos e receberam dietas à base de óleo de soja (controle), oliva, peixe e linhaça ad libitum, por um período de 9 semanas. Foram avaliados os parâmetros bioquímicos (colesterol total, HDLcolesterol e triglicerídeos), contagem de linfócitos na mucosa intestinal e morfometria das vilosidades. O grupo alimentado com óleo de peixe apresentou menores valores de colesterol total, HDL-colesterol e triglicerídeos (p<0,05). Os grupos tratados com óleo de peixe e oliva apresentaram melhor preservação das vilosidades intestinais. Menor deposição de linfócitos na mucosa ileal foi verificada no grupo linhaça (p<0.001). A partir destes resultados foi desenvolvido um segundo experimento com o intuito de responder a hipótese do efeito quimiopreventivo dos óleos (oliva, peixe e linhaça) presentes nas dietas normolipídicas e administradas agora à animais induzidos a lesões pré-neoplásicas. Neste experimento, ratos Wistar adultos foram tratados com 1,2-dimetilhidrazina, na dose de 40mg/kg peso corporal, mantidos nas mesmas condições experimentais anteriores. Foi avaliado o perfil de ácidos graxos do soro, tecido hepático, gordura intra-abdominal e nas fezes; investigada a presença de aminas bioativas no tecido hepático, mediadores inflamatórios (IL-8, MCP-1 e TGF-β) na mucosa colônica, realizada a contagem de linfócitos na mucosa intestinal e morfometria das vilosidades. Verificou-se que o grupo alimentado com óleo de peixe apresentou maiores níveis de EPA (p=0,004) e DHA (p<0,001) no fígado e maiores níveis do ácido linolênico (p=0,003) e EPA (p=0,011) no tecido adiposo intra-abdominal em relação aos demais tratamentos. Nestes tecidos, menor relação ω6/ω3 foi verificada nos grupos alimentados com óleos poliinsaturados (peixe e linhaça). Maiores níveis de ácido α-linolênico foi excretado pelo grupo linhaça (p=0,014). Não foi encontrada diferença no número de FCA entre os grupos alimentados com as diferentes fontes lipídicas (p>0,05). Não houve diferença na expressão de IL-8, TGF-β, e MCP-1 em relação ao controle (p>0,05). Ao avaliar comparativamente a expressão das citocinas, verificamos que o grupo peixe expressou duas vezes mais TGF-β e oito vezes menos IL-8 em relação aos demais tratamentos).O grupo oliva apresentou menores níveis de espermidina (p=0,008) em relação aos demais tratamentos. O grupo alimentado com óleo de peixe apresentou menor deposição de linfócitos na mucosa ileal (p<0,001). A análise morfométrica mostrou que os tratamentos apresentaram altura de vilosidade, profundidade de cripta e largura de vilosidade menores que o controle (p<0,001). Este estudo demonstrou que os óleos de linhaça, oliva e peixe apresentam diferentes respostas em relação ao óleo de soja na preservação da mucosa intestinal e proliferação de linfócitos em ratos Wistar saudáveis. Em animais tratados com carcinógeno, o óleo de peixe apresentou um importante efeito protetor a mucosa colônica. Os ácidos graxos α-linolênico, EPA e DHA apresentaram um metabolismo diferenciado em relação à incorporação nos tecidos hepático e intra-abdominal, à formação de pré-lesões neoplásicas e à expressão de citocinas inflamatórias no cólon. A maior incorporação de PUFA da série ω3 no grupo peixe sugere um efeito modulador da resposta inflamatória, em função da menor migração de linfócitos na mucosa intestinal deste grupo.
The action of oils and fats in human nutrition has been amply studied and discussed in recent decades. Attention has been given to the nutritional quality of these oils, where quantity and composition of fatty acids is important. Essential fatty acids are important due to the their pharmacological roles and as mediators of inflammatory reactions, directly related to immunological resistance, thromboticprocesses and neoplastic diseases. Experimental studies support the hypothesis that ω6 fatty acids contribute to progressive development of neoplastic wounds while ω3 fatty acids possess a protective action. The objective of the present study was to evaluate the effects of adding different oils to the diet (soy, olive, fish, flaxseed) for prevention of preneoplastic wounds on the colon of Wistar rats. Also evaluated was its effect on the lipid profile, inflammatory markers, migration of inflammatory cells and histological analysis of intestinal mucus of the animals. Two experiments were performed. In the first, and exploratory study was performed on adult Wistar rats fed with normolipid diets AIN-93M (4g/100g diet). The animals were divided in four groups and received diets based on soy (control), olive, fish and flaxseed oil ad libitum, for a period of 9 weeks. Biochemical parameters (total cholesterol, HDL-cholesterol and triglycerides), number of lymphocytes in the intestinal mucus and morphometry of the villi were evaluated. The group fed with fish oil presented the lowest values of total cholesterol, HDL-cholesterol and triglycerides (p<0.05). The grouptreated with fish and olive oil presented the best preservation of the intestinal villi. A smaller deposition of lymphocytes in the ileal mucus was verified in the flaxseed group (p<0.001). From these results a second experiment was developed with the intention of confirming the hypothesis of the chemopreventive effect of the oils (olive, fish and flaxseed) present in the normolipid diets and now administered to the animals induced to pre-neoplastic wounds. In this experiment, adult Wistar rats were treated with 1,2-dimethylhydrazine, at the dose of 40 mg/kg body weight, maintained in the same experimental conditions as before. The fatty acid profiles of the serum, xvii hepatic tissue, intra-abdominal fat and in the feces were evaluated; investigating the presence of bioactive amines in the hepatic tissue, inflammatory mediators (IL-8, MCP-1 and TGF-β) in the colonial mucus, and counting the lymphocytes in the intestinal mucus and mophometry of the villi. It was verified that the group fed with fish oil presented greater levels of EPA (p=0.004) and DHA (p<0.001) in the liver and greater levels of linolenic acid (p=0.003) and EPA (p=0.011) in the intra-abdominal adipose tissue in relation to the other treatments. In these tissues, a lower ω6/ω3 ratio was verified in the groups fed with polyunsaturated oils (fish and flaxseed). Greater levels of α-linolenic acid were excreted by the flaxseed group (p=0.014). No difference was encountered in the number of FCA between the groups fed with the different lipid sources (p>0.05). There was no difference in the expression of IL-8, TGF-β, and MCP-1 in relation to the control (p>0.05). When comparatively evaluating expression of the cytokines, it was verified that the fish oil group expressed two times more TGF-β and eight times less IL-8 in relation to the other treatments. The olive oil group presented lower levels of spermidine (p=0.008) in relation to the other treatments. The group fed with fish oil presented few deposits of lymphocytes in the ileal mucus (p<0.001). A morphmetric analysis showed that the treatments presented height of the villus, depth of the crypt and width of the villi less than that of the control (p<0.001). This study demonstrated that flaxseed, olive and fish oil presented different responses in relation to soy oil on the preservation of intestinal mucus and proliferation of lymphocytes in healthy Wistar rats. In animals treated with carcinogens, the fish oil presented an important protective effect on the colonial mucus. The α-linolenic fatty acids, EPA and DHA present a differential metabolism in relation to incorporation in the hepatic and intra-abdominal tissues, formation of pre-neoplastic wounds and expression of inflammatory cytokines in the colon. Greater incorporation of PUFA from the ω3 series in the fish oil group suggests a modular effect on the inflammatory response, in function of the lower migration of lymphocytes in the intestinal mucus of this group.
The action of oils and fats in human nutrition has been amply studied and discussed in recent decades. Attention has been given to the nutritional quality of these oils, where quantity and composition of fatty acids is important. Essential fatty acids are important due to the their pharmacological roles and as mediators of inflammatory reactions, directly related to immunological resistance, thromboticprocesses and neoplastic diseases. Experimental studies support the hypothesis that ω6 fatty acids contribute to progressive development of neoplastic wounds while ω3 fatty acids possess a protective action. The objective of the present study was to evaluate the effects of adding different oils to the diet (soy, olive, fish, flaxseed) for prevention of preneoplastic wounds on the colon of Wistar rats. Also evaluated was its effect on the lipid profile, inflammatory markers, migration of inflammatory cells and histological analysis of intestinal mucus of the animals. Two experiments were performed. In the first, and exploratory study was performed on adult Wistar rats fed with normolipid diets AIN-93M (4g/100g diet). The animals were divided in four groups and received diets based on soy (control), olive, fish and flaxseed oil ad libitum, for a period of 9 weeks. Biochemical parameters (total cholesterol, HDL-cholesterol and triglycerides), number of lymphocytes in the intestinal mucus and morphometry of the villi were evaluated. The group fed with fish oil presented the lowest values of total cholesterol, HDL-cholesterol and triglycerides (p<0.05). The grouptreated with fish and olive oil presented the best preservation of the intestinal villi. A smaller deposition of lymphocytes in the ileal mucus was verified in the flaxseed group (p<0.001). From these results a second experiment was developed with the intention of confirming the hypothesis of the chemopreventive effect of the oils (olive, fish and flaxseed) present in the normolipid diets and now administered to the animals induced to pre-neoplastic wounds. In this experiment, adult Wistar rats were treated with 1,2-dimethylhydrazine, at the dose of 40 mg/kg body weight, maintained in the same experimental conditions as before. The fatty acid profiles of the serum, xvii hepatic tissue, intra-abdominal fat and in the feces were evaluated; investigating the presence of bioactive amines in the hepatic tissue, inflammatory mediators (IL-8, MCP-1 and TGF-β) in the colonial mucus, and counting the lymphocytes in the intestinal mucus and mophometry of the villi. It was verified that the group fed with fish oil presented greater levels of EPA (p=0.004) and DHA (p<0.001) in the liver and greater levels of linolenic acid (p=0.003) and EPA (p=0.011) in the intra-abdominal adipose tissue in relation to the other treatments. In these tissues, a lower ω6/ω3 ratio was verified in the groups fed with polyunsaturated oils (fish and flaxseed). Greater levels of α-linolenic acid were excreted by the flaxseed group (p=0.014). No difference was encountered in the number of FCA between the groups fed with the different lipid sources (p>0.05). There was no difference in the expression of IL-8, TGF-β, and MCP-1 in relation to the control (p>0.05). When comparatively evaluating expression of the cytokines, it was verified that the fish oil group expressed two times more TGF-β and eight times less IL-8 in relation to the other treatments. The olive oil group presented lower levels of spermidine (p=0.008) in relation to the other treatments. The group fed with fish oil presented few deposits of lymphocytes in the ileal mucus (p<0.001). A morphmetric analysis showed that the treatments presented height of the villus, depth of the crypt and width of the villi less than that of the control (p<0.001). This study demonstrated that flaxseed, olive and fish oil presented different responses in relation to soy oil on the preservation of intestinal mucus and proliferation of lymphocytes in healthy Wistar rats. In animals treated with carcinogens, the fish oil presented an important protective effect on the colonial mucus. The α-linolenic fatty acids, EPA and DHA present a differential metabolism in relation to incorporation in the hepatic and intra-abdominal tissues, formation of pre-neoplastic wounds and expression of inflammatory cytokines in the colon. Greater incorporation of PUFA from the ω3 series in the fish oil group suggests a modular effect on the inflammatory response, in function of the lower migration of lymphocytes in the intestinal mucus of this group.
Descrição
Palavras-chave
Óleo de peixe, Óleo de linhaça, Fish oil, Flaxseed oil