RESUMO
Background: The intestinal mucosa is commonly exposed to oxidant nutrients and carcinogens, which can lead to the generation of free radicals. The antioxidants present in the diet assume great importance as possible protective agents, reducing the oxidative damage. In this way, we evaluated the antioxidant action of grape juice on preneoplastic lesions induced by azoxymethane (AOM) in Wistar rats. Methods: The colorectal carcinogenesis was induced by two intraperitoneal injections of 15mg/kg of AOM in Wistar rats. The animals were divided in 7 groups and treated with 1 and 2% concentrations of grape juice before and after carcinogen administration. After euthanasia, the expression of antioxidant enzymes catalase (CAT), copper-zinc superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase (Mn-SOD) CAT, SOD1 and SOD2 were evaluated by immunohistochemistry. Results: AOM decreased the expression of CAT and Mn-SOD enzymes, but not for Cu/Zn-SOD. We observed an increase expression of CAT and Mn-SOD after grape juice administration in some concentrations according to the time of administration of the grape juice before the carcinogen or just after the carcinogen. Conclusion: Our results suggest an independent action of each enzyme and a possible antioxidant action of the grape juice components in the diet being able to balance the body to neutralize the superoxide radicals and not leave them in the cell-damaging form.
Assuntos
Carcinogênese/efeitos dos fármacos , Catalase/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/prevenção & controle , Superóxido Dismutase/metabolismo , Vitis/química , Animais , Antioxidantes/farmacologia , Azoximetano/farmacologia , Carcinogênese/induzido quimicamente , Carcinógenos/farmacologia , Neoplasias Colorretais/induzido quimicamente , Sucos de Frutas e Vegetais , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Oxidantes/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Colorectal cancer is the third most common cancer worldwide in both sexes, with similar geographic patterns between genders. This neoplasm has good prognosis if the disease is diagnosed at early stages. The aim of this study was to evaluate the effect of red grape juice on the expression of COX-2 and Ki-67 expression following colon carcinogenesis induced by azoxymethane (AOM). Thirty-five rats were randomly distributed into seven groups (n=5 per group): G1: SHAM or negative control received only saline; G2 (positive control): animals received 15 mg/kg AOM; G3: animals received 1% red grape juice 2 weeks before the administration of AOM; G4: animals received 2% red grape juice 2 weeks before the administration of AOM; G5: animals received 1% red grape juice 4 weeks after the last administration of AOM; G6: animals received 2% red grape juice 4 weeks after the last administration of AOM; G7: animals received only 2% red grape juice. COX-2 mRNA expression was reduced in animals treated with 1% red grape juice before AOM induction or 2% red grape juice after AOM induction. COX-2 immunoexpression was also reduced to groups treated with red grape juice at 1% before and after AOM induction or 2% red grape juice after AOM induction. Decreased immunoexpression of Ki-67 positive cells was observed in animals treated with 1% grape juice before AOM-treated animals. Taken together, grape juice concentrate is able to exert some chemopreventive activity on rat colon carcinogenesis.
Assuntos
Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/prevenção & controle , Extratos Vegetais/administração & dosagem , Vitis/química , Animais , Azoximetano , Neoplasias do Colo/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Sucos de Frutas e Vegetais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
UNLABELLED: The aim of this study was to evaluate the effects of grape juice on colon carcinogenesis induced by azoxymethane (AOM) and expression of NF-kB, iNOS and TNF- α. METHODS: Forty male Wistar rats were divided into 7 groups: G1, control; G2, 15 mg/kg AOM; G3, 1% grape juice 2 weeks before AOM; G4, 2% grape juice 2 weeks before AOM; G5, 1% grape juice 4 weeks after AOM; G6, 2% grape juice 4 weeks after AOM; G7, 2% grape juice without AOM. Histological changes and aberrant crypt foci (ACF) were studied, while RNA expression of NF- kB, TNF- and iNOS was evaluated by qPCR. RESULTS: The number of ACF was higher in G2, and G4 presented a smaller number of crypts per focus than G5 (p=0.009) and G6. Small ACF (1-3) were more frequent in G4 compared to G2, G5 and G6 (p=0.009, p=0.009 and p=0.041, respectively). RNA expression of NF-kB was lower in G3 and G4 compared to G2 (p=0.004 and p=0.002, respectively). A positive correlation was observed between TNF- α and NF-kB gene expression (p=0.002). In conclusion, the administration of 2% grape juice before AOM reduced the crypt multiplicity, attenuating carcinogenesis. Lower expression of NF-kB was observed in animals exposed to grape juice for a longer period of time, regardless of concentration.
Assuntos
Focos de Criptas Aberrantes/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Ciclo-Oxigenase 2/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , NF-kappa B/genética , Fator de Necrose Tumoral alfa/genética , Vitis/química , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/genética , Focos de Criptas Aberrantes/patologia , Animais , Apoptose/efeitos dos fármacos , Azoximetano/toxicidade , Carcinógenos/toxicidade , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Masculino , Fitoterapia , Extratos Vegetais , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , RNA Mensageiro/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais CultivadasRESUMO
OBJECTIVES: The aim of this study was to evaluate if grape juice concentrate is able to protect against experimental colon carcinogenesis. MATERIAL AND METHODS: For this purpose, a total of 35 male Wistar rats were randomly distributed into seven groups: G1: SHAM animals receiving only saline; G2: animals receiving 15 mg/kg azoxymethane (AOM); G3: animals receiving 1% grape juice concentrate 2 weeks before the administration of AOM; G4: animals receiving 2% grape juice concentrate 2 weeks before the administration of AOM; G5: animals receiving 1% grape juice concentrate 4 weeks after the last administration of AOM; G6: animals receiving 2% grape juice concentrate 4 weeks after the last administration of AOM; G7: animals receiving only 2% grape juice concentrate. RESULTS: The group that received 2% grape juice concentrate before induction with AOM showed the decreased expression of Bcl-2 compared to those animals that were induced by AOM (positive control). Regarding Bax, animals that received grape juice at 2% decreased Bax immunoexpression when compared to AOM group. Furthermore, animals that intake grape juice at 1% after induced by AOM decreased Bax immunoexpression as well. 8-OHdGLI did not show significant statistically differences (p > 0.05) among groups. CONCLUSION: In summary, our results demonstrate that grape juice is able to modulate rat colon carcinogenesis as a result of induction of apoptosis.
Assuntos
Anticarcinógenos/farmacologia , Apoptose/efeitos dos fármacos , Azoximetano , Colo/efeitos dos fármacos , Neoplasias do Colo/prevenção & controle , Sucos de Frutas e Vegetais , Estresse Oxidativo/efeitos dos fármacos , Vitis , 8-Hidroxi-2'-Desoxiguanosina , Animais , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Colo/metabolismo , Colo/patologia , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Modelos Animais de Doenças , Frutas , Masculino , Fitoterapia , Plantas Medicinais , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Wistar , Fatores de Tempo , Proteína X Associada a bcl-2/metabolismoRESUMO
CONTEXT: Genomic alterations play important roles in gastric cancer carcinogenesis. Cyclooxygenases (COX) are important enzymes in the maintenance of mucosal integrity and in pathological processes, mainly in inflammation and cancer. The -765G>C COX-2 polymorphism has been implicated in gastric cancer risk. OBJECTIVES: To evaluate the COX-2 gene polymorphism as a predictor of gastric cancer risk. METHODS: One hundred gastric cancer patients and 150 controls were enrolled from a Brazilian centre. Personal data regarding related risk factors, including alcohol consumption and smoking behavior, were collected via questionnaire. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism. RESULTS: G/G, G/C and C/C genotypes frequencies was 42.7%, 50% and 7.3%, respectively in controls and 59.0%, 34.0% and 7.0% in gastric cancer. The frequency of the genotypes differed between the groups (P = 0.033). A higher risk of gastric cancer was associated with COX-2 -765G/G genotype (P = 0.048; OR:1.98, 95% CI = 1.01-3.90). Alcohol consumption and smoking in patients with -765G/G genotype also increased the risk of gastric cancer. CONCLUSIONS: The -765G/G genotype and the -765G allele had been associated with an increased risk for gastric cancer. The presence of smoking and alcohol consumption increased the risk for gastric cancer in subjects with -765G/G genotype compared with the control group. Polymorphism of COX-2 gene and gastric cancer risk.
Assuntos
Ciclo-Oxigenase 2/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias Gástricas/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Fatores de RiscoRESUMO
Context Genomic alterations play important roles in gastric cancer carcinogenesis. Cyclooxygenases (COX) are important enzymes in the maintenance of mucosal integrity and in pathological processes, mainly in inflammation and cancer. The -765G>C COX-2 polymorphism has been implicated in gastric cancer risk. Objectives To evaluate the COX-2 gene polymorphism as a predictor of gastric cancer risk. Methods One hundred gastric cancer patients and 150 controls were enrolled from a Brazilian centre. Personal data regarding related risk factors, including alcohol consumption and smoking behavior, were collected via questionnaire. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism. Results G/G, G/C and C/C genotypes frequencies was 42.7%, 50% and 7.3%, respectively in controls and 59.0%, 34.0% and 7.0% in gastric cancer. The frequency of the genotypes differed between the groups (P = 0.033). A higher risk of gastric cancer was associated with COX-2 -765G/G genotype (P = 0.048; OR:1.98, 95% CI = 1.01-3.90). Alcohol consumption and smoking in patients with -765G/G genotype also increased the risk of gastric cancer. Conclusions The -765G/G genotype and the -765G allele had been associated with an increased risk for gastric cancer. The presence of smoking and alcohol consumption increased the risk for gastric cancer in subjects with -765G/G genotype compared with the control group. Polymorphism of COX-2 gene and gastric cancer risk. .
Contexto As alterações genômicas tem um papel importante na carcinogênese do câncer gástrico. As cicloxigenases (COX) são enzimas importantes na integridade da mucosa a nos processos patológicos, principalmente na inflamação e no câncer. O polimorfismo -765G>C COX- 2 pode se relacionar ao risco de câncer gástrico. Objetivos Avaliar o polimorfismo de COX-2 como um preditivo de risco de câncer gástrico. Métodos Cem pacientes com câncer gástrico e 150 controles foram estudados provenientes de um centro no Brasil. Foram coletados dados referentes ao consumo de álcool e fumo, considerados fatores de risco. O DNA foi extraído de sangue periférico e os genótipos foram analisados por PCR- RFLP. Resultados As frequências dos genótipos G/G, G/C e C/C foram 42,7%, 50% e 7,3%, respectivamente nos controles e 59,0%, 34,0% e 7,0% no câncer gástrico. A frequência dos genótipos diferiu entre os grupos (P = 0,033). O genótipo -765G/G COX-2 esteve associado a um maior risco de câncer gástrico (P = 0,048; OR:1,98, 95% CI = 1,01-3,90). O consumo de álcool e o fumo em pacientes com o genótipo -765G/G COX-2 também aumentou o risco de câncer gástrico. Conclusões O genótipo -765G/G e o alelo -765G foi associado a maior risco de câncer gástrico. O fumo e o etilismo aumentaram o risco de câncer gástrico em indivíduos com o genótipo -765G/G comparados com o grupo controle. .