RESUMO
Arbutin is utilized in traditional remedies to cure numerous syndromes because of its anti-microbial, antioxidant, and anti-inflammatory properties. This study aimed to evaluate chemopreventive effects of arbutin on azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) in rats. Five groups of rats were used: normal control group (rats injected hypodermically with sterile phosphate-buffered saline once per week for two weeks) and groups 2-5, which were subcutaneously inoculated with 15 mg/kg AOM once a week for two weeks. AOM control and 5-fluorouracil (5-FU) control groups were fed 10% Tween orally daily for 8 weeks using a feeding tube. The treated groups were fed 30 and 60 mg/kg arbutin every day for 2 months. ACF from the AOM control group had aberrant nuclei in addition to multilayered cells and an absence of goblet cells. The negative control group displayed spherical cells and nuclei in basal positions. Histological examination revealed a reduced number of AFC cells from colon tissues of the 5-FU reference group. Arbutin-fed animals showed down-regulation of proliferating cell nuclear antigen (PCNA) and up-regulation of Bax protein compared to AOM control. Rats fed with arbutin displayed a significant increase of superoxide dismutase (SOD) and catalase (CAT) activities in colon tissue homogenates compared to the AOM control group. In conclusion, arbutin showed therapeutic effects against colorectal cancer, explained by its ability to significantly decrease ACF, down-regulate PCNA protein, and up-regulate Bax protein. In addition, arbutin significantly increased SOD and CAT, and decreased malondialdehyde (MDA) levels, which might be due to its anti-proliferative and antioxidant properties.
Assuntos
Focos de Criptas Aberrantes , Arbutina , Azoximetano , Antígeno Nuclear de Célula em Proliferação , Proteína X Associada a bcl-2 , Animais , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/patologia , Focos de Criptas Aberrantes/prevenção & controle , Focos de Criptas Aberrantes/tratamento farmacológico , Antígeno Nuclear de Célula em Proliferação/metabolismo , Masculino , Arbutina/farmacologia , Ratos , Proteína X Associada a bcl-2/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Ratos Wistar , Fluoruracila , CarcinógenosRESUMO
OBJECTIVE: The study's aim was to evaluate Brazilian Brown Propolis (BBP) and Artepillin C (ARC) chemopreventive action in Wistar rats' colons. METHODS: Fifty male Wistar rats were divided into ten experimental groups, including control groups, groups with and without 1,2-dimethylhydrazine (DMH) induction, and BBP, ARC, and ARC enriched fraction (EFR) treatments, for sixteen weeks. Aberrant crypt foci (ACF) were classified as hyperplastic or dysplastic, and proliferating cell nuclear antigen (PCNA) expression was quantified. RESULT: ACF amounts in experimental groups (induced or not) decreased in both colon portions, while the isolated Aberrant Crypt (AC) number increased. Experimental groups of animals showed higher hyperplasia and dysplasia amounts compared with control groups. The ACF dysplastic amount present in groups induced and treated, in both colon portions, had similar values to IDMH (DMH induction group without treatment). In addition, DMH was effective in ACF inducing and there was positive staining for PCNA in basal and upper dysplastic foci portions in all experimental groups, in the mitotic index (MI) evaluation. To conclude, considering all the experimental groups, the one treated with EFR (fraction enriched with ARC) had the lowest rates of cell proliferation. CONCLUSION: BBP and its derivatives prevented crypt cell clonal expansion.
Assuntos
Focos de Criptas Aberrantes , Antineoplásicos , Neoplasias do Colo , Fenilpropionatos , Própole , Ratos , Animais , Masculino , Ratos Wistar , Neoplasias do Colo/tratamento farmacológico , Antígeno Nuclear de Célula em Proliferação/metabolismo , Própole/farmacologia , Própole/uso terapêutico , 1,2-Dimetilidrazina/toxicidade , Brasil , Focos de Criptas Aberrantes/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , CarcinógenosRESUMO
Colorectal cancer, which is the third leading cause of cancer-related deaths worldwide, is a multistep disease, featuring preneoplastic aberrant crypt foci (ACF) as the early morphological manifestation. The roles of hemichannel-forming transmembrane Pannexin 1 (Panx1) protein have not been investigated in the context of colon carcinogenesis yet, although it has contrasting roles in other cancer types. Thus, this study was conducted to examine the effects of Panx1 knockout (Panx1-/- ) on the early events of chemically induced colon carcinogenesis in mouse. Wild type (WT) and Panx1-/- female C57BL6J mice were submitted to a chemically induced model of colon carcinogenesis by receiving six intraperitoneal administrations of 1,2-dimethylhydrazine (DMH) carcinogen. Animals were euthanized 8 h (week 7) or 30 weeks (week 37) after the last DMH administration in order to evaluate sub-acute colon toxicity outcomes or the burden of ACF, respectively. At week 7, Panx1 genetic ablation increased DMH-induced genotoxicity in peripheral blood cells, malondialdehyde levels in the colon, and apoptosis (cleaved caspase-3) in colonic crypts. Of note, at week 37, Panx1-/- animals showed an increase in aberrant crypts (AC), ACF mean number, and ACF multiplicity (AC per ACF) by 56%, 57% and 20%, respectively. In essence, our findings indicate that Panx1 genetic ablation promotes preneoplastic ACF development during chemically induced mouse colon carcinogenesis, and a protective role of Panx1 is postulated.
Assuntos
Focos de Criptas Aberrantes , Neoplasias do Colo , Lesões Pré-Cancerosas , Camundongos , Feminino , Animais , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/genética , 1,2-Dimetilidrazina/efeitos adversos , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Carcinogênese/induzido quimicamente , Carcinogênese/genética , Colo , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/genética , Proteínas do Tecido Nervoso/efeitos adversos , Conexinas/genética , Conexinas/farmacologiaRESUMO
Colorectal cancer is the third most diagnosed cancer worldwide and linked to dietary/lifestyle factors. Arthrospira (Spirulina) platensis (AP) contains bioactive compounds with beneficial effects in vivo/in vitro. We evaluated the effects of AP feeding against 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Male Sprague Dawley rats were given subcutaneous injections of DMH (4 × 40 mg/kg body weight) (G1-G3) or vehicle (G4-G5) twice a week (weeks 3-4). During weeks 1-4, animals were fed a diet containing 1 % (G2) or 2 % (G3-G4) AP powder (w/w). After this period, all groups received a balanced diet until week 12. Some animals were euthanised after the last DMH injection (week 4) for histological, immunohistochemical (Ki-67, γ-H2AX and caspase-3) and molecular analyses (real time-PCR for 91 genes), while other animals were euthanised at week 12 for preneoplastic aberrant crypt foci (ACF) analysis. Both AP treatments (G2-G3) significantly decreased the DMH-induced increase in γ-H2AX (DNA damage) and caspase 3 (DNA damage-induced cell death) in colonic crypts at week 4. In addition, Cyp2e1 (Drug metabolism), Notch1, Notch2 and Jag1 genes (Notch pathway) and Atm, Wee1, Chek2, Mgmt, Ogg1 and Xrcc6 genes (DNA repair) were also down-regulated by 2 % AP feeding (G3) at week 4. A significant reduction in ACF development was observed in both AP-treated groups (G2-G3) at week 12. In conclusion, findings indicate that AP feeding reduced acute colonic damage after DMH, resulting in fewer preneoplastic lesions. Our study provided mechanistic insights on dietary AP-preventive effects against early colon carcinogenesis.
Assuntos
Focos de Criptas Aberrantes , Neoplasias do Colo , Lesões Pré-Cancerosas , Spirulina , Ratos , Animais , Masculino , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/prevenção & controle , 1,2-Dimetilidrazina/toxicidade , Ratos Sprague-Dawley , Carcinogênese/patologia , Colo , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/prevenção & controle , Carcinógenos/toxicidade , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/prevenção & controleRESUMO
Melastoma malabathricum (M. malabathricum) extracts have been reported to exert various pharmacological activities including antioxidants, anti-inflammatory and antiproliferative activities. The objective of the present study was to determine the anticarcinogenic activity of its methanol extract (MEMM) against the azoxymethane (AOM)-induced early colon carcinogenesis in rats. Rats were randomly assigned to five groups (n=6) namely normal control, negative control, and treatment (50, 250 or 500 mg/kg of MEMM) groups. Colon tissues were harvested for histopathological analysis and endogenous antioxidant system determination. MEMM was also subjected to HPLC analysis. Findings showed that MEMM significantly (p<0.05) reversed the AOM-induced carcinogenicity by: i) reducing the formation of aberrant crypt foci (ACF) in colon tissues, and; ii) enhancing the endogenous antioxidant activity (catalase, superoxide dismutase and glutathione peroxidase). Moreover, various phenolics has been identified in MEMM. In conclusion, MEMM exerts the in vivo anticarcinogenic activity via the activation of endogenous antioxidant system and synergistic action of phenolics.
Se ha informado que los extractos de Melastoma malabathricum (M. malabathricum) ejercen diversas actividades farmacológicas, incluidas actividades antioxidantes, antiinflamatorias y antiproliferativas. El objetivo del presente estudio fue determinar la actividad anticancerígena de su extracto de metanol (MEMM) contra la carcinogénesis de colon temprana inducida por azoximetano (AOM) en ratas. Las ratas se asignaron al azar a cinco grupos (n=6), a saber, los grupos de control normal, control negativo y tratamiento (50, 250 o 500 mg/kg de MEMM). Tejidos de colon fueron recolectados para análisis histopatológico y determinación del sistema antioxidante endógeno. MEMM también se sometió a análisis de HPLC. Los hallazgos mostraron que MEMM invirtió significativamente (p<0.05) la carcinogenicidad inducida por AOM al: i) reducir la formación de focos de criptas aberrantes (ACF) en los tejidos del colon, y; ii) potenciar la actividad antioxidante endógena (catalasa, superóxido dismutasa y glutatión peroxidasa). Además, se han identificado varios fenólicos en MEMM. En conclusión, MEMM ejerce la actividad anticancerígena in vivo mediante la activación del sistema antioxidante endógeno y la acción sinérgica de los fenólicos.
Assuntos
Animais , Ratos , Extratos Vegetais/administração & dosagem , Anticarcinógenos/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Melastomataceae/química , Tamanho do Órgão/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ratos Sprague-Dawley , Colo/patologia , Folhas de Planta , Metanol , Compostos Fenólicos , Focos de Criptas Aberrantes , Carcinogênese/efeitos dos fármacos , AntioxidantesRESUMO
BACKGROUND: Colorectal cancer is a highly prevalent disease, requiring effective strategies for prevention and treatment. The present research aimed to formulate a natural fiber-rich food product (NFRFP) and to evaluate its safety, toxicogenetics, and effects on aberrant crypt foci induced by 1,2-dimethyl-hydrazine in a preclinical model. METHODS: A total of 78 male Wistar rats were distributed in six experimental groups: negative control, positive control (1,2-Dimethylhydrazine-40 mg/Kg), and four groups fed with 10% NFRFP: NFRFP, pre-treatment protocol, simultaneous treatment, and post-treatment protocol. RESULTS: The NFRFP was shown to be a good source of fibers and did not change biometric, biochemical, hematological, and inflammatory parameters, and did not induce signs of toxicity and genotoxicity/carcinogenicity. NFRFP exhibited a chemopreventive effect, in all protocols, with damage reduction (% DR) of 75% in the comet test. NFRFP reduced the incidence of aberrant crypt outbreaks by 49.36% in the post-treatment protocol. CONCLUSIONS: The results suggest the applicability of NFRFP in the human diet due to potential production at an industrial scale and easy technological application in different products, since it could be incorporated in food without altering or causing small changes in final product sensory characteristics.
Assuntos
Focos de Criptas Aberrantes/prevenção & controle , Colo/patologia , Neoplasias Colorretais/prevenção & controle , Fibras na Dieta/administração & dosagem , 1,2-Dimetilidrazina , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/metabolismo , Focos de Criptas Aberrantes/patologia , Ração Animal , Animais , Colo/metabolismo , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Citocinas/sangue , Modelos Animais de Doenças , Mediadores da Inflamação/sangue , Masculino , Ratos WistarRESUMO
The present report was designed to determine the antioxidant and antigenotoxic effects of phaseolin (isolated from Phaseolus vulgaris) against mouse colon and liver damage induced by azoxymethane (AOM) and its colon chemopreventive effect. Eight groups with 12 mice each were utilized for an eight-week experiment: the control group was intragastrically (ig) administered 0.9% saline solution; the positive control group was intraperitoneally (ip) injected with 7.5 mg/kg AOM twice a week (weeks three and four of the experiment); three groups were ig administered each day with phaseolin (40, 200, and 400 mg/kg); and three groups were ig administered phaseolin daily (40, 200, and 400 mg/kg) plus 7.5 mg/kg AOM twice a week in weeks three and four of the experiment. The results showed that phaseolin did not produce oxidative stress, DNA damage, or aberrant crypts; in contrast, 100% inhibition of lipoperoxidation, protein oxidation, and nitrites induction generated by AOM was found in both organs, and DPPH radical capture occurred. The two highest phaseolin doses reduced DNA damage induced by AOM in both organs by more than 90% and reduced the AOM-induced aberrant crypts by 84%. Therefore, our study demonstrated the strong in vivo antioxidant, antigenotoxic, and chemopreventive potential of phaseolin.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Colite/prevenção & controle , Phaseolus/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Focos de Criptas Aberrantes/prevenção & controle , Animais , Antioxidantes , Azoximetano , Quimioprevenção , Colite/induzido quimicamente , Colo , Dano ao DNA/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Camundongos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sementes/químicaRESUMO
INTRODUCTION: Aberrant Crypt (AC) and Aberrant Crypt Focus (ACF) are considered pre-neoplasic lesions, ranging from hyperplasia to different degrees of dysplasia in the colon. This work aimed to evaluate and quantify the chemopreventive activity of Zingiber officinale essential oil in the colorectal region of Wistar rats. MATERIALS AND METHODS: We extracted the essential oil from ginger rhizomes and carried out ACF induction, in rats, with 1.2 Dimethylhydrazine (DMH) at a 20 mg/kg dose. The experimental groups were GI (negative control); GII (positive induction control); GIII (DMH + essential oil); GIV (DMH +5-Florouracil) and GV (essential oil). The histological techniques used were methylene blue, hematoxylin-eosin (HE) dyeing, and immunohistochemistry (IHQ). RESULTS: The major essential oil compounds were citral (17.25%), δ-citral (10.25%), camphene (9.55%), α-zingiberene (7.57%), nerol (6.37%) and plelandrene (6.83%). For the presence of AC or ACF, we did not observe them in GI and GV, while in GII and GIII, they were observed, in high values, in both regions, but only in the distal region, there was a significant difference between them. For GIV, for both regions, there were significant lower numbers of AC when compared to GIII. As observed, with HE, there were hyperplastic and dysplastic ACF in the proximal and distal portions of the colon. For IHQ analyses, there were positively PCNA antibody marked cells in all experimental groups. Yet, there was no significant correlation of mitotic index among them. Moreover, the results of GIII compared to GIV were very similar. CONCLUSION: In this sense, the Zingiber officinale essential oil has good antioxidant potential because it presents a mixture of monoterpene and sesquiterpene compounds. Thus, it is able to develop a chemoprotective effect, as it presented similar results to the standard drug, showing cell proliferation control.
Assuntos
1,2-Dimetilidrazina/toxicidade , Focos de Criptas Aberrantes/tratamento farmacológico , Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Óleos Voláteis/farmacologia , Zingiber officinale/química , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/patologia , Animais , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/patologia , Masculino , Ratos , Ratos WistarRESUMO
Antioxidants present in food can act as a protective factor against the development of colorectal cancer (CRC) by reducing the development of aberrant crypt foci (ACF). This study aimed to analyze the effects of supplementation with juçara fruit pulp on the number of ACF and the SOD1 expression in an experimental model of CRC. Colorectal carcinogenesis was induced with 1,2-dimethylhydrazine (DMH) in 16 young female rats (Rattus norvegicus) given a diet supplemented with either juçara fruit pulp (DMH+/juçara+) or control (DMH+/juçara-). Five animals were used as a negative control (DMH-/juçara-). The (DMH+/juçara+) group received 14 days of supplementation (100 ml/animal/day) at 2-day intervals for 1 month. The number of ACF, area of positive staining for SOD1, and SOD1 expression score were evaluated. The (DMH+/juçara+) group presented a lower number of ACF, ACF > 3 crypts, and greater SOD1 expression in the colorectal mucosa. Based on the reduction in the number of lesions and possible positive impact on antioxidant enzymes, juçara fruit pulp appears to support the prevention of CRC, opening new possibilities for its use in dietary supplementation, as well as in the development of products and medications for the prevention and treatment of CRC.
Assuntos
Focos de Criptas Aberrantes/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Euterpe , Mucosa Intestinal/enzimologia , Superóxido Dismutase-1/genética , 1,2-Dimetilidrazina , Animais , Carcinogênese , Suplementos Nutricionais , Euterpe/química , Feminino , Ratos , Aumento de PesoRESUMO
Red and processed meat consumption has been strongly related to increase the risk of colorectal cancer (CRC), although its impact is largely unknown. Hemin, an iron-containing porphyrin, is acknowledged as a putative factor of red and processed meat pro-carcinogenic effects. The aim of this study was to investigate the effects of high dietary hemin on the promotion/progression stages of 1,2-dimethylhydrazine (1,2-DMH)-induced colon carcinogenesis. Twenty-four Wistar male rats were given four subcutaneous 1,2-DMH injections and received either balanced diet or balanced diet supplemented with hemin 0.5â¯mmol/kg for 23 weeks. Colon specimens were analyzed for aberrant crypt foci (ACF) and tumor development. Dietary hemin significantly increased ACF number and fecal water cytotoxicity/genotoxicity in Caco-2 cells when compared to 1,2-DMH control group. However, tumor incidence, multiplicity and cell proliferation did not differ between 1,2-DMHâ¯+â¯hemin and 1,2-DMH control group. Gene expression analysis of 91 target-genes revealed that only three genes (Figf, Pik3r5 and Tgfbr2) were down-regulated in the tumors from hemin-fed rats compared to those from 1,2-DMH control group. Therefore, the findings of this study show that high hemin intake promotes mainly DNA damage and ACF development and but does not change the number nor incidence of colon tumors induced by 1,2-DMH in male rats.
Assuntos
Focos de Criptas Aberrantes/induzido quimicamente , Neoplasias do Colo/induzido quimicamente , Dano ao DNA , Hemina/toxicidade , Lesões Pré-Cancerosas/induzido quimicamente , 1,2-Dimetilidrazina , Ração Animal , Animais , Células CACO-2 , Cocarcinogênese , Ensaio Cometa , Regulação para Baixo/efeitos dos fármacos , Fezes , Humanos , Masculino , Fosfatidilinositol 3-Quinase/genética , Ratos , Ratos Wistar , Receptor do Fator de Crescimento Transformador beta Tipo II/biossíntese , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Carne Vermelha , Fatores de Tempo , Fator D de Crescimento do Endotélio Vascular/biossíntese , Fator D de Crescimento do Endotélio Vascular/genéticaRESUMO
Aberrant crypt foci (ACF) is the precursor lesion of colorectal carcinogenesis (CRC), one of the most common malignancies in the world. Many studies have reported that people with higher phytochemical intake are at a reduced risk of developing ACF. One example of the botanical potential of preventive plant products is Cnidoscolus aconitifolius (CA), commonly known as Chaya. This study evaluated the phenolic profile of CA and the effects of the daily consumption of CA leaf infusion on the formation of ACF, histopathological lesions, and molecular biomarkers after azoxymethane (AOM) and dextran sulfate sodium (DSS) induced premalignant colon lesions in rats treated with for 16 and 32 weeks. The phenolic composition of the CA infusion was identified by reversed phase-high performance liquid chromatography-diode array detection (RP-HPCC-DAD). After sacrifice, a 4 cm segment was collected from the distal part of the colon and stained with methylene blue to look for ACF. Furthermore, 4 µm of colon, liver, and kidney was collected and stained with hematoxylin and eosin for histopathological analysis, along with 7 µm of colon for immunohistochemistry analysis. Eleven phenolic compounds were identified in the infusions, and ACF formation was reduced by 29.5% at the subchronic and by 64.6% at chronic stages. Lesions on kidney, liver, and colon tissue were also reduced. Our data suggest that CA treatment has preventive effects against AOM-/DSS-induced premalignant colon lesions in colon rats at the promotion level, inhibiting the cell proliferation of early neoplastic lesions and colonic inflammation through the decrease of ß-catenin by 41.8% at the subchronic stage and 29% at the chronic stage, along with a 46.2% reduction of cyclooxygenase 2 (COX-2) at long term, despite a high expression of NF-κB (30.3% at the subchronic stage and 22.8% at the chronic stage).
Assuntos
Focos de Criptas Aberrantes/prevenção & controle , Euphorbiaceae/química , Extratos Vegetais/administração & dosagem , Substâncias Protetoras/administração & dosagem , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/patologia , Animais , Azoximetano/efeitos adversos , Colo/efeitos dos fármacos , Colo/patologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Humanos , Masculino , Extratos Vegetais/química , Folhas de Planta/química , Substâncias Protetoras/química , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: Callistemon citrinus (Curtis) Skeels is a shrub native of Australia. In spite of containing an important number of bioactive compounds (1,8-cineole, limonene and α-terpineol) recognized as a potential chemotherapeutic agents, it is only used as an ornamental plant in Mexico. This study investigated the chemopreventive effect of C. citrinus leaves extract on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats. METHODS: Twenty-four rats were divided into 3 groups of eight rats. Group 1 served as negative control, groups 2 and 3 were given subcutaneous injections of DMH (65 mg/kg b.w.) twice a week the first 2 weeks, and then one the third week. In addition, group 3 was administrated with leaves extracts (250 mg/kg b.w., orally daily) during the 22 weeks of the experiment. Animals were killed and the presence of colon tumors and aberrant crypt foci (ACF) were scored for number and distribution pattern along the colon. The activity of two-phase II enzymes quinone reductase (QR) and glutathione S-transferase (GST) was determined in the liver and three segments of the colon: proximal, middle and distal. RESULTS: The results show that rats feed with C. citrinus leaves extract significantly reduced the size of tumors, the number of ACF and the crypt multiplicity. Additionally, C. citrinus leaves extract increased or maintained the activity of QR and GST in the different tissues as compared with DHM-treated group (p > 0.05). CONCLUSION: This study demonstrates that Callistemon citrinus extract could have a chemopreventive effect against colon carcinogenesis.
Assuntos
Neoplasias do Colo/prevenção & controle , Myrtaceae/química , Extratos Vegetais/farmacologia , 1,2-Dimetilidrazina , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/tratamento farmacológico , Focos de Criptas Aberrantes/patologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Peso Corporal/efeitos dos fármacos , Carcinógenos , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Masculino , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
Kefir is a probiotic fermented milk product produced from grains with a complex composition of bacteria and yeasts that live in a symbiotic association. Anti-proliferative, anti-inflammatory, and anti-mutagenic effects are some of the health beneficial properties of kefir grains. The present study was conducted to evaluate whether regular consumption of kefir milk would be capable of preventing the development of pre-neoplastic lesions induced by azoxymethane (AOM). Aberrant crypt foci were induced in BALB-c mice via 2 subcutaneous injections of azoxymethane (15â¯mg/kg) and kefir was administered by daily gavage for 8 weeks (5â¯ml/kg). Additionally, bacterial growth was monitored in pasteurized and ultra-high temperature (UHT) treated milk to compare different fermentation conditions. Our results showed that UHT milk presented better growth of Lactobacillus acidophilus colonies. The aberrant crypt foci were attenuated by approximately 43% (height) and 20% (width) in the kefir group compared to AOM group, suggesting that kefir treatment may contribute to prevent and control the growth of intestinal neoplastic cells.
Assuntos
Focos de Criptas Aberrantes/patologia , Neoplasias Colorretais/patologia , Kefir , Focos de Criptas Aberrantes/induzido quimicamente , Animais , Azoximetano/toxicidade , Carcinógenos/toxicidade , Neoplasias Colorretais/induzido quimicamente , Feminino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Copaiba oleoresins are used in alternative medicine as anti-inflammatory, antitumoral, and antimicrobial treatments. (-)-Copalic acid (CA) is the major diterpene found in exudates from Copaifera species. We have examined the genotoxicity and the chemopreventive potential of Copaifera multijuga oleoresin (CM) and CA. Genotoxicity assessment was examined with the peripheral blood micronucleus test and the comet assay (male Swiss mouse hepatocytes). In the chemoprevention study, we evaluated the effects of CM and CA on the formation of 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in male Wistar rat colon. Neither agent caused a significant increase in micronucleus frequency relative to controls, but the highest CM dose tested (400mg/kg b.w.) caused DNA damage in the comet assay. Both agents significantly reduced the frequency of DMH-induced ACF. Both CM and CA suppressed ACF formation and may have a protective effect against colon carcinogenesis.
Assuntos
Anticarcinógenos/farmacologia , Dano ao DNA , Diterpenos/farmacologia , Fabaceae/química , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Extratos Vegetais/farmacologia , Focos de Criptas Aberrantes/prevenção & controle , Animais , Anticarcinógenos/isolamento & purificação , Anticarcinógenos/toxicidade , Neoplasias do Colo/prevenção & controle , Ensaio Cometa , Diterpenos/isolamento & purificação , Diterpenos/toxicidade , Relação Dose-Resposta a Droga , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Ratos WistarRESUMO
The objective of this study was to evaluate the effect of Moquiniastrum polymorphum ssp floccosum ethanolic extract (MPEE) on 1,2 dimethylhydrazine (DMH)-induced colorectal carcinogenesis in mice. Forty-two male Swiss mice (Mus musculus) were subdivided into six groups (N = 7/group): negative control, DMH, MPEE, pre-treatment, simultaneous, and post-treatment. Results showed that MPEE has antigenotoxic potential on the tested protocols pre- and silmultaneous treatment, and the percent damage reductions (%DRs) were 81.88 and 93.12%, respectively. The micronucleus test demonstrated that MPEE has great antimutagenic activity, with %DRs higher than 77.09 in the associated groups. The aberrant crypt focus assay demonstrated anticarcinogenic potential of MPEE as the associated groups showed %DRs that ranged from 62.13 to 95.14%. The study shows that MPEE is nontoxic and has chemopreventive and anticarcinogenic activity, thus it may prove to be a promising medicinal plant in view of its demonstrated properties.
Assuntos
1,2-Dimetilidrazina/toxicidade , Focos de Criptas Aberrantes/tratamento farmacológico , Asteraceae/química , Neoplasias Colorretais/tratamento farmacológico , Etanol/administração & dosagem , Focos de Criptas Aberrantes/prevenção & controle , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/prevenção & controle , Dano ao DNA/efeitos dos fármacos , Etanol/farmacologia , Masculino , Camundongos , Testes para Micronúcleos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Colorectal cancer is a global public health issue. Studies have pointed to the protective effect of probiotics on colorectal carcinogenesis. Activia® is a lacto probiotic product that is widely consumed all over the world and its beneficial properties are related, mainly, to the lineage of traditional yoghurt bacteria combined with a specific bacillus, DanRegularis, which gives the product a proven capacity to intestinal regulation in humans. The aim of this study was to evaluate the antigenotoxic, antimutagenic, and anticarcinogenic proprieties of the Activia product, in response to damage caused by 1,2-dimethylhydrazine (DMH) in Swiss mice. Activia does not have shown antigenotoxic activity. However, the percent of DNA damage reduction, evaluated by the antimutagenicity assay, ranged from 69.23 to 96.15% indicating effective chemopreventive action. Activia reduced up to 79.82% the induction of aberrant crypt foci by DMH. Facing the results, it is inferred that Activia facilitates the weight loss, prevents DNA damage and pre-cancerous lesions in the intestinal mucosa.
Assuntos
Focos de Criptas Aberrantes/prevenção & controle , Anticarcinógenos/farmacologia , Neoplasias Colorretais/prevenção & controle , Dano ao DNA , Probióticos/farmacologia , Iogurte/microbiologia , 1,2-Dimetilidrazina , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/genética , Focos de Criptas Aberrantes/patologia , Animais , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Suplementos Nutricionais , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , CamundongosRESUMO
Colorectal Cancer (CRC) is the third most frequent type of cancer worldwide. In the past few years, studies have revealed a protective effect of metformin (MET-an anti-hyperglycemic drug, used to treat type 2 diabetes), against CRC. The protective effect of MET has been associated with AMPK activation (and mTOR inhibition), resulting in suppressed protein synthesis, and reduced cell proliferation in malignant transformed cells. To elucidate new mechanisms for the protective effect of metformin, we evaluated the oxidative stress and inflammatory process modulation, since these processes are strictly involved in colorectal carcinogenesis. The present study evaluated the protective effect of MET in a CRC model induced by 1,2-dimethylhydrazine (DMH) in Balb/c female mice. The simultaneous/continuous treatment (administration of MET and DMH simultaneously), revealed protective activity of MET, preventing the formation of aberrant crypt foci (ACF) in 71.4% at distal colon sections, and was able to restore basal labeling of apoptosis. Treatment with MET also reduced the inflammatory process induced by DMH, resulting in of the reduction of oxidative stress and nitric oxide related parameters. © 2016 Wiley Periodicals, Inc.
Assuntos
1,2-Dimetilidrazina/toxicidade , Focos de Criptas Aberrantes/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Metformina/administração & dosagem , Proteínas Quinases Ativadas por AMP/metabolismo , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/imunologia , Focos de Criptas Aberrantes/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Feminino , Metformina/farmacologia , Camundongos , Neoplasias Experimentais , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Resultado do TratamentoRESUMO
ABSTRACT PURPOSE: To evaluate the effects of L-lysine on the intestinal and urothelial epithelium of rats subjected to ureterosigmoidostomy (new model for surgical carcinogenesis). METHODS: Forty-two rats, 9 weeks of age, were divided into 6 groups. Animals in groups A, B, C were subjected to ureterosigmoidostomy (US) and treated with L-lysine, celecoxib and H2O, respectively. Groups D, E and F (non-operated controls) received L-lysine, celecoxib and H2O, respectively. The L-lysine dose was 150 mg/kg and that of celecoxib was 20 mg/kg. The colon was analyzed for the presence of aberrant crypt foci (ACF) under a stereomicroscope.The tissue was stained with hematoxylin and eosin and PAS alcian blue. RESULTS: There were rare ACF, and there was no statistically significant difference between the groups. Histopathologic study of the ureteral epithelium identified moderate to severe urothelial hyperplasia in rats with ureterosigmoidostomy. Transitional hyperplasia in the ureters of animals receiving L-lysine (A) showed an apparent difference compared to the control (C) (P=0.2424). There was no dysplasia or atypia CONCLUSION: L-lysine does not promote carcinogenesis of the intestinal and urethelial epithelium of rats subjected to ureterosigmoidostomy at the doses and times studied.
Assuntos
Animais , Feminino , Ratos , Colo Sigmoide/cirurgia , Estomas Cirúrgicos , Focos de Criptas Aberrantes/patologia , Carcinogênese , Neoplasias Intestinais/etiologia , Lisina/farmacologia , Neoplasias da Bexiga Urinária/etiologia , Ureterostomia/métodos , Ratos Wistar , Modelos Animais de Doenças , Estomas Cirúrgicos/efeitos adversos , Mucosa Intestinal/patologiaRESUMO
The modifying effects of a Western diet (WD) during early life on the susceptibility to colon carcinogenesis induced by dimethylhydrazine (DMH) were examined in male rats as later adults. Three groups were studied: a lifetime control diet-fed group, a test group fed WD since pregnancy from dams until postnatal day (PND) 42, and a group fed WD at adulthood. At PND 70, all groups received the carcinogen DMH and were euthanized 10 wk later. Colonic aberrant crypt foci (ACF) were scored (number and crypt multiplicity) and the altered pattern of ß-catenin expression was evaluated in the colonic lesions. ACF multiplicity (≥4 crypts) was significantly higher in the group fed WD at early life than in the group fed the control diet. ACF number, crypt multiplicity, and the number of high-grade dysplastic lesions were significantly higher in the group fed WD at adulthood than in the groupfed the control diet. The number of lesions with altered ß-catenin expression was higher in the groups receiving WD at early life or at adulthood than in the lifetime control-diet-fed group. These findings indicate that WD exposure at early life increased the susceptibility to colon carcinogenesis at adulthood.
Assuntos
Focos de Criptas Aberrantes/patologia , Neoplasias Colorretais/patologia , Dieta Ocidental/efeitos adversos , Focos de Criptas Aberrantes/induzido quimicamente , Animais , Animais Recém-Nascidos , Carcinogênese/induzido quimicamente , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias Colorretais/induzido quimicamente , Dimetilidrazinas/toxicidade , Suscetibilidade a Doenças , Feminino , Masculino , Cuidado Pós-Natal , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Ratos , beta Catenina/genética , beta Catenina/metabolismoRESUMO
PURPOSE:: To evaluate the effects of L-lysine on the intestinal and urothelial epithelium of rats subjected to ureterosigmoidostomy (new model for surgical carcinogenesis). METHODS:: Forty-two rats, 9 weeks of age, were divided into 6 groups. Animals in groups A, B, C were subjected to ureterosigmoidostomy (US) and treated with L-lysine, celecoxib and H2O, respectively. Groups D, E and F (non-operated controls) received L-lysine, celecoxib and H2O, respectively. The L-lysine dose was 150 mg/kg and that of celecoxib was 20 mg/kg. The colon was analyzed for the presence of aberrant crypt foci (ACF) under a stereomicroscope.The tissue was stained with hematoxylin and eosin and PAS alcian blue. RESULTS:: There were rare ACF, and there was no statistically significant difference between the groups. Histopathologic study of the ureteral epithelium identified moderate to severe urothelial hyperplasia in rats with ureterosigmoidostomy. Transitional hyperplasia in the ureters of animals receiving L-lysine (A) showed an apparent difference compared to the control (C) (P=0.2424). There was no dysplasia or atypia. CONCLUSION:: L-lysine does not promote carcinogenesis of the intestinal and urethelial epithelium of rats subjected to ureterosigmoidostomy at the doses and times studied.