RESUMO
AIMS: Fructooligosaccharides (FOSs) known for their health properties and ß-(2â6)-levan-type FOSs have shown prebiotic and immunomodulatory activities that overcome those of commercial ß-(2â1)-FOSs, but costs do not favour their use. Moreover, FOSs can reach the bloodstream through the diet, and little is known about their direct effect on cells. The aim of this work was to produce high-content FOSs by Bacillus subtilis natto CCT7712 in a bioreactor using commercial sucrose and to evaluate their antiproliferative effects in OVCAR-3 cells. METHODS AND RESULTS: FOS production reached 173·60 g l-1 , 0·2 vvm aeration and uncontrolled pH. Levan-type FOSs, composed of ß-(2 â 6) links and mainly GF3 (6-nystose), were identified using RMN spectroscopy, FT-IR and ESI-MS. FOSs decreased the viability and proliferation of OVCAR-3 cells, and the effects were associated with an increased pro-inflammatory response by the induction of IL-8 and TNF-α, and the repression of ER-ß genes. The metabolic profiles showed disruption of cellular homeostasis that can be associated with a decrease in proliferation. CONCLUSIONS: The high production of levan-type FOSs from B. subtilis natto CCT7712 in a bioreactor was achieved, and they showed antiproliferative potential in OVCAR-3 cells. SIGNIFICANCE AND IMPACT OF THE STUDY: FOS could be a good target for future therapeutic studies and commercial use.
Assuntos
Bacillus subtilis/metabolismo , Proliferação de Células/efeitos dos fármacos , Oligossacarídeos/metabolismo , Oligossacarídeos/farmacologia , Reatores Biológicos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Frutanos/química , Frutanos/metabolismo , Frutanos/farmacologia , Humanos , Oligossacarídeos/química , Sacarose/metabolismoRESUMO
(R)-Goniothalamin (R-GNT) is a secondary metabolite isolated from the plants of the genus Goniothalamus. This molecule has attracted the attention of researchers because of its selective cytotoxicity against tumor cells and its ability to induce apoptosis. (S)-Goniothalamin (S-GNT) is a synthetic enantiomer of R-GNT, and its mechanism of action is largely unknown. In this study, we investigated the activity of S-GNT in a human non-small cell lung cancer NCI-H460 cells. We observed that the cells exposed to this compound exhibited cytotoxicity in a concentration-dependent manner. Based on the data obtained through the assessment of apoptosis induction in situ and the comet assay, we suggest that this cytotoxicity occurs due to the potential ability of this molecule to induce DNA damage with the consequent induction of cell death via apoptosis. A significant reduction in the messenger RNA levels of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) gene that encodes the survivin protein was found. This novel finding may explain the inhibition of cell proliferation and induction of apoptosis in tumor cells caused by this compound.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Dano ao DNA , Regulação para Baixo/efeitos dos fármacos , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Pironas/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Cinética , Dose Letal Mediana , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Mensageiro/metabolismo , Estereoisomerismo , SurvivinaRESUMO
Aflatoxins (AF) and fumonisins (FU) are a major problem faced by poultry farmers, leading to huge economic losses. This experiment was conducted to determine the effects of AF (1 mg/kg of feed) and FU (25 mg/kg of feed), singly or in combination, on the lipid metabolism in commercial layers and investigate the efficacy of a commercial binder (2 kg/t of feed) on reducing the toxic effects of these mycotoxins. A total of 168 Hisex Brown layer hens, 37 wk of age, were randomized into a 3 × 2 + 1 factorial arrangement (3 diets with no binder containing AF, FU, and AF+FU; 3 diets with binder containing AF, FU, and AF+FU; and a control diet with no mycotoxins and binders), totaling 7 treatments. The hens contaminated with AF showed the characteristic effects of aflatoxicosis, such as a yellow liver, resulting from the accumulation of liver fat, lower values of plasma very low-density lipoprotein and triglycerides, and higher relative weight of the kidneys and liver. Hepatotoxic and nephrotoxic effects of FU were not observed in this study. On the other hand, the FU caused a reduction in small intestine length and an increase in abdominal fat deposition. The glucan-based binder prevented some of the deleterious effects of these mycotoxins, particularly the effects of AF on hepatic lipid metabolism, kidney relative weight, and FU in the small intestine.
Assuntos
Aflatoxina B1/toxicidade , Aflatoxinas/toxicidade , Galinhas/metabolismo , Fumonisinas/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Aflatoxina B1/administração & dosagem , Aflatoxinas/administração & dosagem , Ração Animal/análise , Animais , Peso Corporal , Dieta/veterinária , Ingestão de Alimentos , Feminino , Contaminação de Alimentos , Fumonisinas/administração & dosagem , Glucanos/química , OviposiçãoRESUMO
This study investigated the consequences of intrauterine protein restriction on the gastrointestinal tract and particularly on the gene expression and activity of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group) were evaluated at 3 or 16 weeks of age. Maternal protein restriction during pregnancy produced offspring with growth restriction from birth (5.7 ± 0.1 vs 6.3 ± 0.1â g; mean ± SE) to weaning (42.4 ± 1.3 vs 49.1 ± 1.6â g), although at 16 weeks of age their body weight was similar to control (421.7 ± 8.9 and 428.5 ± 8.5â g). Maternal protein restriction also increased lactase activity in the proximal (0.23 ± 0.02 vs 0.15 ± 0.02), medial (0.30 ± 0.06 vs 0.14 ± 0.01) and distal (0.43 ± 0.07 vs 0.07 ± 0.02 U·g-1·min-1) small intestine, and mRNA lactase abundance in the proximal intestine (7.96 ± 1.11 vs 2.38 ± 0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein restriction increased sucrase activity (1.20 ± 0.02 vs 0.91 ± 0.02 U·g-1·min-1) and sucrase mRNA abundance (4.48 ± 0.51 vs 1.95 ± 0.17 relative units) in the duodenum of 16-week-old rats. In conclusion, the present study shows for the first time that intrauterine protein restriction affects gene expression of intestinal enzymes in offspring.
Assuntos
Dieta com Restrição de Proteínas , Dissacaridases/metabolismo , Regulação da Expressão Gênica/fisiologia , Intestino Delgado/enzimologia , Adaptação Fisiológica , Animais , Animais Recém-Nascidos , Dissacaridases/análise , Feminino , Gravidez , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo RealRESUMO
This study investigated the consequences of intrauterine protein restriction on the gastrointestinal tract and particularly on the gene expression and activity of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group) were evaluated at 3 or 16 weeks of age. Maternal protein restriction during pregnancy produced offspring with growth restriction from birth (5.7 ± 0.1 vs 6.3 ± 0.1 g; mean ± SE) to weaning (42.4 ± 1.3 vs 49.1 ± 1.6 g), although at 16 weeks of age their body weight was similar to control (421.7 ± 8.9 and 428.5 ± 8.5 g). Maternal protein restriction also increased lactase activity in the proximal (0.23 ± 0.02 vs 0.15 ± 0.02), medial (0.30 ± 0.06 vs 0.14 ± 0.01) and distal (0.43 ± 0.07 vs 0.07 ± 0.02 U·g-1·min-1) small intestine, and mRNA lactase abundance in the proximal intestine (7.96 ± 1.11 vs 2.38 ± 0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein restriction increased sucrase activity (1.20 ± 0.02 vs 0.91 ± 0.02 U·g-1·min-1) and sucrase mRNA abundance (4.48 ± 0.51 vs 1.95 ± 0.17 relative units) in the duodenum of 16-week-old rats. In conclusion, the present study shows for the first time that intrauterine protein restriction affects gene expression of intestinal enzymes in offspring.
Assuntos
Animais , Feminino , Gravidez , Dieta com Restrição de Proteínas , Dissacaridases/metabolismo , Regulação da Expressão Gênica/fisiologia , Intestino Delgado/enzimologia , Adaptação Fisiológica , Animais Recém-Nascidos , Dissacaridases/análise , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The polysaccharide ß-glucan has biological properties that stimulate the immune system and can prevent chronic pathologies, including cancer. It has been shown to prevent damage to DNA caused by the chemical and physical agents to which humans are exposed. However, the mechanism of ß-glucan remains poorly understood. The objective of the present study was to verify the protective effect of ß-glucan on the expression of the genes ERCC5 (involved in excision repair of DNA damage), CASP9 (involved in apoptosis), and CYP1A1 (involved in the metabolism of xenobiotics) using real-time polymerase chain reaction and perform metabolic profile measurements on the HepG2 cells. Cells were exposed to only benzo[a]pyrene (B[a]P), ß-glucan, or a combination of B[a]P with ß-glucan. The results demonstrated that 50 µg/mL ß-glucan significantly repressed the expression of the ERCC5 gene when compared with the untreated control cells in these conditions. No change was found in the CASP9 transcript level. However, the CYP1A1 gene expression was also induced by HepG2 cells exposed to B[a]P only or in association with ß-glucan, showing its effective protector against damage caused by B[a]P, while HepG2 cells exposed to only ß-glucan did not show CYP1A1 modulation. The metabolic profiles showed moderate bioenergetic metabolism with an increase in the metabolites involved in bioenergetic metabolism (alanine, glutamate, creatine and phosphocholine) in cells treated with ß-glucan and to a lesser extent treated with B[a]P. Thus, these results demonstrate that the chemopreventive activity of ß-glucan may modulate bioenergetic metabolism and gene expression.
Assuntos
Agaricus/química , Caspase 9/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , beta-Glucanas/química , beta-Glucanas/farmacologia , Benzo(a)pireno/toxicidade , Caspase 9/genética , Citocromo P-450 CYP1A1/genética , Dano ao DNA , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Metabolismo Energético , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Proteínas Nucleares/genética , Fatores de Transcrição/genética , TranscriptomaRESUMO
The effects of aflatoxin and fumonisin and their combination on egg production and quality, as well as the efficacy of a mycotoxin adsorbent in reducing or eliminating these effects in commercial layers. A number of 168 layers with initial age of 37 weeks were submitted to an experimental period of 56 days. A completely randomized experimental design in a 3x2+1 factorial arrangement was applied (3 treatments with mycotoxins: aflatoxin (AF), fumonisin (FU), or aflatoxin + fumonisin (AF+FU); 2 treatments with or without adsorbent; and a control group that was fed no mycotoxins, nor adsorbent), totaling 7 treatments with 6 replicated of 4 birds/cage. The dietary inclusion levels were 1ppm AF, 25ppm FU, and 2 kg adsorbent/ton feed. Birds fed AF presented the lowest percentage of lay (p=0.0594). Egg mass was the lowest (p<0.05) in the AF+FU treatment (49.49g). The treatment with AF resulted in higher eggshell thickness and strength (p<0.05) than the FU treatment and the control group. The inclusion of the adsorbent in the AF contaminated feed reduced eggshell strength, which returned to levels similar to those of the control group. The observed changes indicate that aflatoxin is toxic at a concentration of 1ppm, and that the effects of fumonisin were less evident as a function of the low dose applied. The inclusion of the glucan (2kg/ton) effectively reverted some of the toxic effects of aflatoxin and, at lower extension, those of fumonisin, when these mycotoxins were invidually added to commercial layer feeds.
Assuntos
Animais , Galinhas , Ovos/análise , Aflatoxinas , DietaRESUMO
The effects of aflatoxin and fumonisin and their combination on egg production and quality, as well as the efficacy of a mycotoxin adsorbent in reducing or eliminating these effects in commercial layers. A number of 168 layers with initial age of 37 weeks were submitted to an experimental period of 56 days. A completely randomized experimental design in a 3x2+1 factorial arrangement was applied (3 treatments with mycotoxins: aflatoxin (AF), fumonisin (FU), or aflatoxin + fumonisin (AF+FU); 2 treatments with or without adsorbent; and a control group that was fed no mycotoxins, nor adsorbent), totaling 7 treatments with 6 replicated of 4 birds/cage. The dietary inclusion levels were 1ppm AF, 25ppm FU, and 2 kg adsorbent/ton feed. Birds fed AF presented the lowest percentage of lay (p=0.0594). Egg mass was the lowest (p<0.05) in the AF+FU treatment (49.49g). The treatment with AF resulted in higher eggshell thickness and strength (p<0.05) than the FU treatment and the control group. The inclusion of the adsorbent in the AF contaminated feed reduced eggshell strength, which returned to levels similar to those of the control group. The observed changes indicate that aflatoxin is toxic at a concentration of 1ppm, and that the effects of fumonisin were less evident as a function of the low dose applied. The inclusion of the glucan (2kg/ton) effectively reverted some of the toxic effects of aflatoxin and, at lower extension, those of fumonisin, when these mycotoxins were invidually added to commercial layer feeds.(AU)
Assuntos
Animais , Galinhas , Ovos/análise , Dieta , AflatoxinasRESUMO
Propolis is one of the hive products that has been used extensively in folk medicine, due to its several biological and pharmaeological properties. Besides, propolis-containing products have been intensely marketed by the pharmaceutical , industry and health-food stores. This work was carried out in order to investigate whether propolis treatment could revert the metabolic alterations of streptozotocin-induced diabetic rats. Animais were kept in metabolic cages and diabetes was induced by a single dose of streptozotocin (35 mg/kg, IV). After a week, rats with glicemia higher than 230 mg/dL were divided into two groups and treated with ethanolic extract of propolis (10 and 90 mg/kg, PO) for seven days. Glycemia and free fatty acids were determined, as well as food and water intake, body weight and, urine were registered weekly. Data showed no significant differences in the analyzed variables. Based on these results, one may conclude that propolis had no effects after diabetes establishment, in our conditions assays. Further assays with different concentrations of propolis and periods of administration should be carried out in order to evaluate its therapeutic potential in this disease