RESUMEN

Abstract The α-tomatine is a steroidal glycoalkaloid found in immature tomatoes (Lycopersicon esculentum) that has important biological functions including the inhibition of cancer cell growth and preventing metastasis. This study aimed to evaluate the effects of α-tomatine on cytotoxicity, cellular proliferation, apoptosis, and mRNA expression of APC, CCNA2, β-catenin, CASP9, BAK, BAX and BCL-XL in colorectal adenocarcinoma cell line HT-29. HT29 cells were treated with three concentrations of α-tomatine (0.1, 1 and 10 µg/mL), although only the 1 µg/mL concentration of α-tomatine was used to evaluate genetic expression patterns by real time-PCR. Results showed that α-tomatine was cytotoxic only at the 10 µg/mL concentration. Cell proliferation was significantly inhibited after the first 24 hours of treatment only with concentrations of 10 µg/mL. In contrast, there were no significant differences in apoptosis for any treatment. In the gene expression studies, only APC expression was significantly altered by α-tomatine treatment. In conclusion, α-tomatine has antiproliferative activity in the first 24h of treatment, does not induce apoptosis in this cell line and causes disruption of cell membranes, thereby increasing the expression of APC gene related to cell cycle.

Asunto(s)

Tomatina/farmacología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , ARN Mensajero , Neoplasias Colorrectales/patología , Adenocarcinoma/patología , Expresión Génica , Células HT29 , Reacción en Cadena en Tiempo Real de la Polimerasa

RESUMEN

ABSTRACT The study evaluated the effects of brown flaxseed supplementation in natura on the prevention of DNA damage induced by 1,2-dimethylhydrazine (DMH) in vivo. The experimental groups were Negative and Positive Controls and the protocols of Pre-treatment, Simultaneous, Post-treatment, Pre+continuous in relation to the supplementation of brown flaxseed and administration with carcinogenic compound. The results showed that brown flaxseed supplementation does not cause genomic and genetic damage. In addition, brown flaxseed showed a chemopreventive food that reduced the damages assessed by the comet assay up to 94.07x and the damages assessed by the micronucleus assay up to 91.88x. Brown flaxseed supplementation also increased the frequency of monocytes and lymphocytes indicating immunological improvements. Thus, brown flaxseed supplementation is considered safe and reduces the frequency of DNA damage that can lead to tumors. Therefore, if these events are confirmed in humans, flaxseed will have reinforced its indication as a functional chemopreventive food in the prevention of cancer.

RESUMEN

Cardanol is an effective antioxidant and is a compound with antimutagenic and antitumoral activity. Here, we evaluated the genotoxic and mutagenic potential of saturated side chain cardanol and its effects in combination with cyclophosphamide in preventing DNA damage, apoptosis, and immunomodulation. Swiss mice were treated with cardanol (2.5, 5 and 10 mg/kg) alone or in combination with cyclophosphamide (100 mg/kg). The results showed that cardanol is an effective chemopreventive compound, with damage reduction percentages that ranged from 18.9 to 31.76% in the comet assay and from 45 to 97% in the micronucleus assay. Moreover, cardanol has the ability to reduce the frequency of apoptosis induced by cyclophosphamide. The compound did not show immunomodulatory activity. A final interpretation of the data showed that, despite its chemoprotective capacity, cardanol has a tendency to induce DNA damage. Hence, caution is needed if this compound is used as a chemopreventive agent. Also, this compound is likely not suitable as an adjuvant in chemotherapy treatments that use cyclophosphamide.

RESUMEN

CONTEXT: Annona crassiflora Mart. (Annonaceae) is a medicinal plant that is widely used in folk medicine, which leads to its investigation as a potential source of new pharmacological principles. OBJECTIVE: This study describes the anti-inflammatory, antiallodynic, and antimutagenic/chemopreventive activities of the leaves A. crassiflora methanolic extract. Its antimutagenic mode of action was analyzed in a plant or animal experimental model. MATERIALS AND METHODS: Total flavonoids were quantified by spectrophotometry at 415 nm and its composition was analyzed by (1)H NMR spectra. Animals received orally, 30, 100, and 300 mg/kg of extract in both tests, carrageenan-induced paw edema and myeloperoxidase activity. Animals were treated with 100 and 300 mg/kg, in all the analyzed tests, pleural cell migration and protein exudation, carrageenan-induced cell migration into the pouch, induction of joint inflammation and carrageenan-induced allodynia response in the mouse paw. To evaluate the antimutagenic/chemopreventive activity through the Allium cepa test, we used 5, 10, and 15 mg/L of extract, and for the micronucleus test in the peripheral blood, we used the dose of 15 mg/kg. RESULTS: The fractionation of the ethyl acetate (EA) fraction, resulting from the partition of the methanol extract of the A. crassiflora, afforded through chromatographic methods resulted in the isolation of kaempferol 3-O-ß-glucoside and kaempferol 3-O-ß-diglucoside. Oral treatment with 100 and 300 mg/kg of extract significantly inhibited the carrageenan-induced edema formation, with inhibitions of 53 ± 7% and 47 ± 10%; in MPO activity, the observed inhibitions were 60 ± 7% for 100 mg/kg treatment and 63 ± 7% for 300 mg/kg. The ACME reduced significantly the total leukocytes (an inhibition of 78 ± 9% with 100 mg/kg and 90 ± 7% with 300 mg/kg) and protein levels (approximately 100% inhibition with both doses) in the pleurisy model. In carrageenan-induced leukocyte migration into the pouch, the extract inhibited leukocyte migration only when administered 300 mg/kg per dose (the reduction was 43 ± 5%). Pretreatment with extract failed to reduce the zymosan-induced edema formation and did not inhibit the carrageenan-induced mechanical allodynia. Damage reduction in Allium cepa tested with different concentrations (5, 10, and 15 mg/L) was 66.17, 75.75, and 69.19% for the pre-treatment; 72.72, 33.33, and 22.22% for the simple simultaneous treatment; 100.50, 93.93, and 102.52% for the simultaneous treatment with pre-incubation; 89.39, 79.79, and 84.34%; for the post-treatment, and 86.36, 81.31, and 93.43% for the continuous treatment. The antimutagenic evaluation in the micronucleous test showed a damage reduction of 75.00 and 64.58% for the pre-treatment and simultaneous protocols, respectively. The post-treatment protocol increased the cyclophosphamide effects in 45.83%. CONCLUSION: These results suggest that this medicinal plant has chemopreventive and anti-inflammatory therapeutic potential.

Asunto(s)

Analgésicos/farmacología , Annona/química , Antiinflamatorios/farmacología , Anticarcinógenos/farmacología , Antimutagênicos/farmacología , Hiperalgesia/prevención & control , Inflamación/prevención & control , Metanol/química , Micronúcleos con Defecto Cromosómico/efectos de los fármacos , Extractos Vegetales/farmacología , Solventes/química , Analgésicos/química , Analgésicos/aislamiento & purificación , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Anticarcinógenos/química , Anticarcinógenos/aislamiento & purificación , Antimutagênicos/química , Antimutagênicos/aislamiento & purificación , Carragenina , Quimiotaxis de Leucocito/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Hiperalgesia/inducido químicamente , Inflamación/inducido químicamente , Inflamación/inmunología , Masculino , Ratones , Pruebas de Micronúcleos , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta , Plantas Medicinales , Espectroscopía de Protones por Resonancia Magnética , Factores de Tiempo

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Byrsonima verbascifolia is used in folk medicine to treat diarrhea, intestinal infections, chronic wounds, Chagas disease, inflammation and as a diuretic. However there is no investigation regarding the Byrsonima verbascifolia hydrometanolic extract (BVHME) used during gestation. MATERIALS AND METHODS: The pregnant females were randomly divided into 5 groups. Control group received saline plus DMSO (1%) in a volume of 0.1 mL/10 g (b.w.), via gavage, for at least 15 days prior to mating and throughout the gestational period. The Pre-treatment group received the BVHME, via gavage, at a dose of 50 mg/kg (b.w.) for at least 15 days prior to mating and up to the appearance of the vaginal plug. The Organogenesis group received the BVHME at a dose of 50 mg/kg (b.w.), via gavage, on the 5-15th gestational day. The Gestational group received the BVHME at a dose of 50 mg/kg (b.w.), via gavage, throughout the gestational period (from the 1st to the 18th day of pregnancy). The Pre+Gestational group received the BVHME at a dose of 50mg/kg (b.w.), via gavage, for at least 15 days prior to mating and up to throughout the gestational period. The clinical signals of maternal and fetuses toxicity were evaluated, as the mutagenicity and immunomodulation tests were performed. RESULTS AND CONCLUSIONS: The present investigation shows, for the first time, that the use of Byrsonima verbascifolia extract in pregnant Swiss mice, did not alter the female reproductive function, mutagenicity or immunostimulation as well as not interfere with embryofetal development at least in our experimental conditions.

Asunto(s)

Desarrollo Embrionario/efectos de los fármacos , Desarrollo Fetal/efectos de los fármacos , Malpighiaceae , Intercambio Materno-Fetal , Extractos Vegetales/toxicidad , Reproducción/efectos de los fármacos , Animales , Recuento de Células Sanguíneas , Femenino , Inmunomodulación , Ratones , Pruebas de Micronúcleos , Fagocitosis/efectos de los fármacos , Hojas de la Planta , Embarazo , Bazo/citología

RESUMEN

The development of various types of cancer results from the interaction among endogenous, environmental and hormonal factors, where the most notable of these factors is diet. The aim of the present study was to determine the antigenotoxic, anticarcinogenic, phagocytic and immunomodulatory activities of Agaricus blazei. The test antigenotoxicity (Comet Assay) and anticarcinogenic (Test of Aberrant Crypt Foci) assess changes in DNA and/or intestinal mucosa that correlate to cancer development. Tests of phagocytosis in the spleen and differential count in blood cells allow the inference of modulation of the immune system as well as to propose a way of eliminating cells with DNA damage. Supplementation with the mushroom was carried out under pre-treatment, simultaneous treatment, post-treatment and pre-treatment+continuous conditions. Statistical analysis demonstrated that the mushroom did not have genotoxic activity but showed antigenotoxic activity. Supplementation caused an increase in the number of monocytes and in phagocytic activity, suggesting that supplementation increases a proliferation of monocytes, consequently increasing phagocytic capacity especially in the groups pre-treatment, simultaneous and pre-treatment+continuous. The data suggest that A. blazei could act as a functional food capable of promoting immunomodulation which can account for the destruction of cells with DNA alterations that correlate with the development of cancer, since this mushroom was demonstrated to have a preventive effect against pre-neoplastic colorectal lesions evaluated by the aberrant crypt foci assay. According to these results and the literature, it is believed that supplementation with A. blazei can be an efficient method for the prevention of cancer as well as possibly being an important coadjuvant treatment in chemotherapy.

Asunto(s)

Agaricus , Antimutagênicos/farmacología , Antineoplásicos/farmacología , Factores Inmunológicos/fisiología , Fagocitosis/efectos de los fármacos , Fagocitosis/fisiología , Extractos Vegetales/farmacología , Agaricus/genética , Agaricus/inmunología , Animales , Antimutagênicos/aislamiento & purificación , Antimutagênicos/metabolismo , Antineoplásicos/sangre , Antineoplásicos/aislamiento & purificación , Ensayo Cometa/métodos , Daño del ADN/efectos de los fármacos , Daño del ADN/fisiología , Factores Inmunológicos/sangre , Factores Inmunológicos/aislamiento & purificación , Masculino , Ratones , Extractos Vegetales/sangre , Extractos Vegetales/aislamiento & purificación

RESUMEN

This study aimed to evaluate the quimiopreventive ability of phenylalanine. We used pregnant and non-pregnant female mice divided into the following groups: G1-PBS, (0.1 mL/kg b.w); G2, cyclophosphamide (35 mg/kg p.c.-i.p.); G3 and G4, phenylalanine (150 and 300 mg/kg b.w respectively-v.o.) and G5 and G6, association between the two doses of phenylalanine and cyclophosphamide, respectively. The peripheral blood samples were taken at T0, before the administration of any drug test and / or vehicles, also at T24 and T48 where the collections were made 24 and 48 h after administration of cyclophosphamide, respectively. A general analysis has found that, for the group of non-pregnant female, the antimutagenic evaluation showed reduction percentages of damage of 57.24 percent and 31.64 percent for G5 and G6, respectively, at T24, and 29.32 percent and 24.13 percent for G5 and G6, respectively, at T48. Antimutagenic pregnant animals in the 24 h quimiopreventive efficiency shown only for the lower dose (G5) and the percentages of reduction were 43.25 percent in G5 and G6 at 18.47 percent. At T48 the harm-reduction percentages were 44.67 percent and 37.76 percent for G5 and G6, respectively.

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A presente pesquisa teve por objetivo avaliar a capacidade quimiopreventiva da fenilalanina. Utilizou-se um lote de fêmeas prenhes e não prenhes divididas nos seguintes grupos experimentais: G1, PBS (0,1 mL/kg p.c.); G2, ciclofosfamida (35 mg/kg p.c.-i.p.); G3, fenilalanina (150 mg/kg p.c.-v.o.) e G4, fenilalanina (300 mg/kg p.c.-v.o.) e G5 (150 mg/kg p.c. de fenilalanina e 35 mg/kg de ciclofosfamida); G6, (300 mg/kg p.c. de fenilalanina e 35 mg/kg de ciclofosfamida). As coletas de sangue periférico foram realizadas em T0, antes da administração de qualquer substância teste e/ou veículos, e igualmente em T24 e T48, onde as coletas foram realizadas respectivamente 24 e 48 h após a administração da ciclofosfamida. Em uma análise geral verificou-se que, para o grupo de fêmeas não prenhes, a avaliação da antimutagenicidade demonstrou porcentagens de redução de danos de 57,24 por cento e 31,64 por cento para G5 e G6, respectivamente, em T24, e 29,32 por cento e 24,13 por cento para G5 e G6, respectivamente, em T48. Nos animais prenhes a antimutagenicidade de 24 h demonstrou eficiência quimiopreventiva apenas para a menor dose (G5) e as porcentagens de redução de danos foram de 43,25 por cento em G5 e 18,47 por cento em G6. No momento T48 as porcentagens de redução de danos foram de 44,67 por cento e 37,76 por cento para G5 e G6, respectivamente.

RESUMEN

A presente pesquisa avaliou a ação mutagênica e antimutagênica de um biopolímero de glucose extraído da Agrobacterium radiobacter (Biopolímero de Agrobacterium radiobacter). O experimento foi realizado com camundongos Swiss machos divididos em oito grupos. O tratamento com o biopolímero foi realizado por gavage em dose única concomitante a uma dose de solução tampão fosfato nos grupos de avaliação da mutagenicidade, ou ao agente indutor de danos no DNA, ciclofosfamida, na concentração de 50 mg/kg (peso corpóreo - p.c.), nos grupos de avaliação da antimutagenicidade. Utilizou-se o teste de micronúcleo em sangue periférico e a coleta de sangue foi realizada 24 e 48 h após a aplicação das substâncias-teste. A análise estatística demonstrou que o biopolímero não possui atividade mutagênica e que é efetivo em prevenir danos no DNA. As porcentagens de redução de danos nos grupos de antimutagenicidade foram de 83,9 por cento, 89,1 por cento e 103,1 por cento em 24 h e 101,24 por cento, 98,14 por cento e 120,64 por cento em 48 h para as doses de 75, 150 e 300mg/kg (p.c.), respectivamente. A alta porcentagem de redução de danos associada à ausência de efeitos mutagênicos indica, além da atividade quimioprotetora, a possibilidade do biopolímero ser um alimento funcional candidato à utilização como co-adjuvante na quimioterapia para prevenir efeitos colaterais.

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This study evaluated the mutagenic and ant mutagenic action of a biopolymer of glucose extracted from Agrobacterium radiobacter (Biopolymer of Agrobacterium radiobacter). The experiment was conducted with Swiss male mice divided into eight groups. Treatment with the biopolymer was performed in a single dose by gavage at a dose of concomitant phosphate buffer groups in the evaluation of mutagenicity, or the agent of inducing DNA damage, cyclophosphamide, the concentration of 50 mg/kg (body weight --b.w.), in groups of assessment ant mutagenic. We used the micronucleus test in peripheral blood. The blood sample was held 24 and 48 h after application of the test substances. Statistical analysis showed that the biopolymer has no mutagenic activity and it is effective in preventing damage to DNA. The percentages of damage reduction in groups of ant mutagenic were 83.9 percent, 89.1 percent and 103.1 percent in 24 h and 101.24 percent, 98.14 percent and 120.64 percent at doses of 48 to 75, 150 and 300 mg/kg (b.w.) respectively. The high percentage of damage reduction associated with the absence of mutagenic effects indicates the possibility of biopolymer chemoprotection action. It can also be considered a functional food candidate to be used as co-adjuvant chemotherapy to prevent side effects.