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Toxic metals that are released into aquatic environments from natural and anthropogenic sources are absorbed by aquatic organisms and may threaten the health of both aquatic organisms and humans. Despite this, there have been limited studies on the metal concentrations in fish and humans in Central Asia. This study summarizes the presence of the toxic metals arsenic (As), mercury (Hg), cadmium (Cd), and lead (Pb) in aquatic bodies, fish, and seafood products and conducts a risk assessment. While certain areas show a notable increase in fish and seafood consumption, the overall intake in Central Asia remains below recommended levels. However, in regions with high fish consumption, there is a potential for elevated exposure to toxic metals, especially Hg. The risk of exposure to toxic metals in fish and seafood in Central Asia emerges as a significant concern. Comprehensive monitoring, regulation, and remediation efforts are imperative to ensure the safety of water sources and food consumption in the region. Public awareness campaigns and the establishment of dietary guidelines play a crucial role in minimizing the health risks associated with consumption.
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Arsénico , Mercurio , Metales Pesados , Animales , Humanos , Alimentos Marinos/análisis , Mercurio/toxicidad , Mercurio/análisis , Metales/toxicidad , Cadmio/toxicidad , Arsénico/toxicidad , Arsénico/análisis , Peces , Asia , Metales Pesados/toxicidad , Metales Pesados/análisis , Medición de Riesgo , Contaminación de Alimentos/análisisRESUMEN
The pseudocereal buckwheat is one of the ancient domesticated crops. The aim of the present review was to outline the potential of buckwheat as an agricultural crop and brings studies on buckwheat into a new larger perspective combining current knowledge in agricultural history and practice, nutritional and sensory properties, as well as possible benefits to human health. Historically, buckwheat was an appreciated crop because of its short growth period, moderate requirements for growth conditions, and high adaptability to adverse environments. Nowadays, interest in buckwheat-based food has increased because of its nutritional composition and many beneficial properties for human health. Buckwheat is a rich course of proteins, dietary fibers, vitamins, minerals, and bioactive compounds, including flavonoids. Moreover, it contains no gluten and can be used in the production of gluten-free foods for individuals diagnosed with celiac disease, non-celiac gluten sensitivity, or wheat protein allergies. Buckwheat is traditionally used in the production of various foods and can be successfully incorporated into various new food formulations with positive effects on their nutritional value and attractive sensory properties. Further research is needed to optimize buckwheat-based food development and understand the mechanism of the health effects of buckwheat consumption on human well-being.
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The anticoagulant drug warfarin is used treat atrial fibrillation. Several cases of drug-drug and drug-food interactions have been reported for warfarin.The aim of this study was to investigate the interaction between simultaneous administration of warfarin with the two ubiquitous flavonoids quercetin and curcumin.Using porcine primary hepatocytes we demonstrated that warfarin treatment increased the mRNA and protein expression of CYP3A(29), while no changes in CYP1A2 were observed. Co-treatment with quercetin and/or curcumin decreased the warfarin-induced CYP3A protein expression. Moreover, when quercetin and curcumin were co-administrated to warfarin-exposed hepatocytes the protein expression of CYP1A2 was decreased. In hepatic microsomes, curcumin inhibited the activity of both CYP1A2 and CYP3A, while warfarin had no effect. Both quercetin and curcumin decreased the CYP1A2 and CYP3A activity when co-administrated with warfarin.The results clearly demonstrated that quercetin and curcumin can cause food-drug interactions with warfarin, and that the cocktail effect of exposure to more compounds than one can further enhance these interactions.
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Curcumina , Citocromo P-450 CYP1A2 , Animales , Citocromo P-450 CYP3A , Sistema Enzimático del Citocromo P-450 , Microsomas Hepáticos , Quercetina , Porcinos , WarfarinaRESUMEN
Background: Meat and dairy products are important ingredients in Kazakhstan, although there are indications that high consumption of red and processed meat is associated with a risk of several non-communicable diseases and has an adverse impact on the environment. Aim: The aim of this study was to investigate the dietary habits of young adults in Kazakhstan, particularly meat and fish consumption frequency among university students in five regions of Kazakhstan. Methods: The assessment of meat and fish consumption was based on the food frequency questionnaire. Region of residence, age, sex, weight, height and parental education were also self-reported. Results: Meat consumption among the participants was lower than recommended consumption of 1500 g per week in Kazakhstan but almost two-fold higher than the World Cancer Research Fund recommendations of 500 g per week. Approximately 24% of the participants reported to consume meat every day. Only 8.6% of the participants reported fish consumption in line with the recommendation of approximately 270 g per week in Kazakhstan. Meat and fish consumption was fairly homogeneous across regions and sex. Conclusion: The results from this study contribute to the relatively limited information on meat and fish consumption in Kazakhstan. Further knowledge on dietary habits and probably improved nutrition recommendations on meat consumption in Kazakhstan are needed to protect public health and the environment.
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BACKGROUND: Despite their vulnerability to the toxic effects of certain metals, biomonitoring data on adolescents are limited. In the present study, we assessed blood concentrations of toxic metals (cadmium [Cd], total mercury [Hg], and lead [Pb] in a national representative sample of Swedish adolescents. We also examined the associations of Cd, total Hg and Pb with habitual intakes of major energy-providing food groups and other possible determinants such as age, sex, household education, Nordic or non-Nordic origin, and smoking. METHODS: We analysed blood concentrations of Cd, total Hg, and Pb in a sample of 1099 adolescents from the Riksmaten Adolescents 2016-17 study in three age groups (mean age of 12, 15, and 18 years) using inductively coupled plasma mass spectrometry. The participants completed web-based questionnaires on food consumption frequency, sociodemographic factors and health status. Dietary data from two web-based 24-h dietary recalls were used to estimate the habitual intake of 10 major food groups. RESULTS: Almost all participants had detectable concentrations of Cd, total Hg, and Pb in whole blood. The median blood concentrations were 0.12 µg/L for Cd, 0.72 µg/L for total Hg, and 7.1 µg/L for Pb. Higher blood concentrations of Cd were observed in girls than in boys, whereas concentrations of total Hg and Pb were higher in boys. We observed an inverse association between Cd and meat intake. Total Hg concentrations were positively associated with intakes of fish, eggs, meat, and vegetables, and Pb concentrations were inversely associated with intakes of dairy products. Furthermore, smokers had higher concentrations of Cd and Pb. CONCLUSIONS: We found that fish was a potentially important source of exposure to total Hg in Swedish adolescents. No other food group was identified to have a strong impact on the blood levels of Cd, total Hg and Pb. Thirteen per cent of the adolescents had blood Pb concentrations above 12 µg/L, the reference point used in the risk assessment of Pb by the European Food Safety Authority (EFSA).
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Cadmio , Mercurio , Adolescente , Animales , Cadmio/análisis , Niño , Dieta , Femenino , Humanos , Plomo , Masculino , Mercurio/análisis , Fumar , Suecia/epidemiologíaRESUMEN
Water from wastewater treatment plants contains concentrations of pharmaceutically active compounds as high as micrograms per liter, which can adversely affect fish health and behavior, and contaminate the food chain. Here, we tested the ability of the common carp hepatic S9 fraction to produce the main metabolites from citalopram, metoprolol, sertraline, and venlafaxine. Metabolism in fish S9 fractions was compared to that in sheep. The metabolism of citalopram was further studied in fish. Our results suggest a large difference in the rate of metabolites formation between fish and sheep. Fish hepatic S9 fractions do not show an ability to form metabolites from venlafaxine, which was also the case for sheep. Citalopram, metoprolol, and sertraline were metabolized by both fish and sheep S9. Citalopram showed concentration-dependent N-desmethylcitalopram formation with Vmax = 1781 pmol/min/mg and Km = 29.7 µM. The presence of ellipticine, a specific CYP1A inhibitor, in the incubations reduced the formation of N-desmethylcitalopram by 30-100% depending on the applied concentration. These findings suggest that CYP1A is the major enzyme contributing to the formation of N-desmethylcitalopram. In summary, the results from the present in vitro study suggest that common carp can form the major metabolites of citalopram, metoprolol, and sertraline.
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Citalopram/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Metoprolol/metabolismo , Microsomas Hepáticos/metabolismo , Preparaciones Farmacéuticas/metabolismo , Sertralina/metabolismo , Clorhidrato de Venlafaxina/metabolismo , Animales , Carpas , Femenino , Técnicas In Vitro , Masculino , OvinosRESUMEN
The fatty acid (FA) composition of raw, salted, and fermented fish products prepared from two populations of Baikal omul (Coregonus autumnalis migratorius) was determined. Total lipid content in the raw, salted, and fermented fish products was 3.85, 4.04, and 3.76%, respectively. Overall, the most abundant fatty acids were 14:0 (myristic acid), 16:0 (palmitic acid), 16:1n-7 (palmitoleic acid), 18:1n-9 (oleic acid), 20:5n-3 (eicosapentaenoic acid), and 22:6n-3 (docosahexaenoic acid, DHA). Polyunsaturated FAs were the main fatty acid group. Among unsaturated FA, n-3 forms dominated. The highest amounts of n-3 FAs were found in raw fish, followed by fermented and salted fish. Salting significantly increased the content of some FAs (15:0, 16:2n-4, 18:3n-3, 20:3n-3) compared with raw fish and decreased the DHA content. The FA composition of fermented fish did not differ from that of raw fish. The n-3:n-6 ratio did not differ between raw, salted, and fermented fish from population A, while the ratio was higher in raw fish from population B. Overall, thiobarbituric acid reactive substances, and thereby oxidation, were significantly lower in raw fish than in salted and fermented fish. Salting, but not fermentation, affected the FA composition of fish.
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1. Humans and animals are commonly exposed to indole-3-carbinol (I3C) and resveratrol (RES) via food or beverages. Moreover, these compounds have been demonstrated to potentially cause food-drug interactions. However, information about their combined effects is limited. Therefore, we investigated the effects of I3C and RES, both as single compounds and in combination, on cytochrome P450 1A and 3A activity and gene expression. 2. Using porcine microsomes, we demonstrated that RES caused non-competitive inhibition of CYP1A activity and un-competitive inhibition of CYP3A activity. Compared to the effect of single compounds, co-treatment with I3C and RES increased a degree of inhibition of CYP1A activity. 3. In porcine primary hepatocytes, treatment with I3C and RES resulted in induction of CYP1A1, CYP1A2 and CYP3A29 mRNA expression. 4. In conclusion, we demonstrated that both RES and I3C could cause food-drug interactions and that the combined effect could be more potent in doing so.
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Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP3A/metabolismo , Indoles/farmacología , Estilbenos/farmacología , Animales , Citocromo P-450 CYP1A1/antagonistas & inhibidores , Citocromo P-450 CYP3A/genética , Inhibidores del Citocromo P-450 CYP3A/farmacología , Interacciones Alimento-Droga , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Receptor X de Pregnano , Receptores de Hidrocarburo de Aril/genética , Receptores de Esteroides/genética , Resveratrol , PorcinosRESUMEN
Monitoring the contamination level in aquatic environments and assessing the impact on aquatic life occurs throughout the world. In the present study, an approach based on a combination of biomarkers and the distribution of various industrial and municipal pollutants was used to investigate the effect of aquatic environmental contamination on fish. Monitoring was performed in ten rivers in the Czech Republic (Berounka, Dyje, Elbe, Luznice, Odra, Ohre, Otava, Sázava, Svratka, and Vltava rivers, with one or two locations in each river) at the same sites that were regularly monitored within the Czech National Monitoring Program in 2007-2011. Health status, hepatic ethoxyresorufin-O-deethylase (EROD) activity, total cytochrome P450 content, and the plasma vitellogenin concentration were assessed in wild chub (Squalius cephalus) males caught at the monitored sites. The contamination level was the highest in the Svratka River downstream of Brno. Among all measured persistent organic pollutants (POPs), polychlorinated biphenyls and dichlorodiphenyltrichloroethane and its metabolites were the major contributors of POPs in fish muscle. Elbe, Odra, and Svratka rivers were identified as the most polluted. Fish from these locations showed reduced gonad size, increased vitellogenin concentration in male plasma, EROD, and total cytochrome P450 content. These biomarkers can be used for future environmental monitoring assessments. Overall, this study improves our understanding of the relationship between human activities and pollutant loads and further contributes to the decision to support local watershed managers to protect water quality in this region.
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Cyprinidae , Monitoreo del Ambiente , Ríos/química , Contaminantes Químicos del Agua/análisis , Animales , Biomarcadores/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , República Checa , DDT/análisis , Contaminación Ambiental , Peces/metabolismo , Hidrocarburos Clorados/análisis , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Bifenilos Policlorados/análisis , Análisis de Componente Principal , Vitelogeninas/sangre , Calidad del AguaRESUMEN
Sourdough fermentation is considered to have beneficial effects on postprandial satiety and metabolic responses, but studies demonstrating effects at physiological conditions are lacking. The aim of this acute breakfast intervention study was to determine the effect of consumption of sourdough-fermented and unfermented rye crispbread on self-rated appetite, postprandial glucose and insulin response in healthy subjects. In all, twenty-four Swedish adults were included in a single-blinded, randomised cross-over trial. Three crispbreads (sourdough-fermented and unfermented whole grain rye and yeast-fermented refined wheat as control) were consumed as part of a standardised breakfast. Subjective appetite score, assessed using visual analogue scale, and plasma glucose and insulin concentrations were measured at baseline and postprandially until 360 and 240 min, respectively. Structural changes and viscosity during mastication and gastric digestion were investigated using in vitro methods. Hunger and desire to eat were lower (P<0·05) based on AUC measurements after intake of sourdough-fermented rye crispbread compared with after intake of yeast-fermented refined wheat crispbread. On the basis of AUC (0-230 min), insulin response was lowest after intake of unfermented rye crispbread compared with sourdough-fermented rye and yeast-fermented refined wheat crispbread. Degradation of viscous fibres and faster bolus disintegration for the sourdough-fermented bread may partly explain the less favourable metabolic responses compared with unfermented bread. Our results showed that food processing affects the composition and structural characteristics of rye bread, which has implications for appetite and metabolic responses.
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Apetito , Glucemia/metabolismo , Pan , Alimentos Fermentados , Periodo Posprandial , Secale/química , Adulto , Desayuno , Estudios Cruzados , Fibras de la Dieta/administración & dosificación , Digestión , Femenino , Péptido 1 Similar al Glucagón/sangre , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Saciedad , Método Simple Ciego , Suecia , Triticum/química , Granos Enteros/química , Adulto JovenRESUMEN
1. Little is known about the activities and regulation of cytochrome P4503A (CYP3A) enzymes in porcine colon in response to specific feeding components. 2. We added hydrolyzable tannins to the diet of fattening boars and studied its effect on the expression of hepatic and intestinal CYP3A. 3. In total, 51 Landrace × Large White boars were assigned to the following treatment groups: control (without the addition of hydrolysable tannins), T1 (diet-containing 1% hydrolysable tannin extract), T2 (diet-containing 2% hydrolysable tannin extract) and T3 (diet-containing 3% hydrolysable tannin extract). CYP3A expression and activity were measured in microsomes prepared from liver and colon tissue. 4. CYP3A protein expression and activity were increased in the colon of pigs fed 2% and 3% tannins, while no changes were observed with lower tannin concentrations, or in the liver of any treatment groups. Also, it was demonstrated that colon mucosa possess CYP3A activity similar to that measured in the liver. 5. The present results provide the first evidence that tannin supplementation can modulate CYP3A in porcine colon mucosa in vivo. The physiological significance of this finding for the health status of the individual animal needs further investigation.
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1. This study examined hepatic cytochrome P450 (CYP450) response to dietary sesamin in combination with different n-6/n-3 fatty acid ratios in fish diet. Over a period of 4 months, fish were fed seven different experimental diets an n-6/n-3 FA ratio of either 0.5 or 1.0 in combination with two sesamin levels: low sesamin = 1.16 g/kg feed and high sesamin = 5.8 g/kg feed. Control diets did not contain sesamin. 2. The CYP450-associated activities of ethoxyresorufin O-deethylase (EROD), 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylation (BFCOD), pentoxyresorufin O-depentylase (PROD), coumarin hydroxylase (COH), methoxyresorufin O-deethylase (MROD) and p-nitrophenol hydroxylase (PNPH) were significantly induced by dietary sesamin in a dose-related manner. 3. Expressions of the genes CYP1A1, CYP1A3, CYP3A, AhR1α, AhR2ß, AhR2δ and PXR involved in the regulation of CYP450 activities, was not the primary source of this induction.
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Sistema Enzimático del Citocromo P-450/metabolismo , Dioxoles/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Lignanos/farmacología , Salmo salar/metabolismo , Xenobióticos/metabolismo , Animales , Aceites de Pescado/farmacología , Hígado/efectos de los fármacos , Hígado/enzimología , Aceites de Plantas/farmacologíaRESUMEN
In vitro impacts of five organic solvents on cytochrome P450 (CYP450) enzyme activity were investigated using hepatic microsomes of rainbow trout. The rates of several CYP450-mediated reactions were investigated at solvent concentrations ranging from 0.01% to 3%. The solvents greatly affected all tested reactions. In at least 0.8% ethanol, 2% methanol or acetone, 1% acetonitrile or 3% dimethyl sulfoxide (DMSO), 7-ethoxyresorufin-O-deethylase (EROD) activity decreased and at 3% acetonitrile or ethanol, it was undetected. At 3%, all tested solvents except methanol reduced 7-benzyloxy-4-trifluoromethylcoumarin-O-debenzylase (BFCOD) activity, but at low concentrations of ethanol (2% and lower) or DMSO (1% and lower), it was induced. This was not seen with the inclusion of a pre-incubation step. p-Nitrophenolhydroxylase (PNPH) activity was not affected at concentrations below 1% DMSO, and at 2% acetonitrile it was reduced, as it was above 1% methanol or 0.5% ethanol. Acetone did not affect PNPH activity with or without a pre-incubation step. In general, the degree of inhibition was similar with and without the pre-incubation step. We conclude that the concentration of organic solvent for solubilizing the substrate and inhibitor in in vitro microsomal studies should be minimized.
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Acetona/farmacología , Acetonitrilos/farmacología , Sistema Enzimático del Citocromo P-450/metabolismo , Dimetilsulfóxido/farmacología , Etanol/farmacología , Hígado/enzimología , Metanol/farmacología , Microsomas Hepáticos/efectos de los fármacos , Oncorhynchus mykiss/metabolismo , Solventes/farmacología , Animales , Relación Dosis-Respuesta a Droga , Isoenzimas , Cinética , Hígado/efectos de los fármacos , Microsomas Hepáticos/enzimología , Especificidad por SustratoRESUMEN
Faba beans, rich in protein and ideal for Swedish cultivation, are limited in food industry use due to anti-nutritional factors (ANFs) that hinder nutrient absorption. An extraction method was developed in our study to mitigate ANFs in faba beans, using aqueous alkaline methods and isoelectric precipitation with differential salt concentration. This method yielded 15.8 g of protein per 100 g of flour, with a protein concentration exceeding 83% of the total extract. It reduced ANFs like phytic acid (28.0%), lectins (87.5%), vicine (98.5%), and convicine (99.7%). Extraction conditions were optimized using response surface methodology, identifying pH 6, 2 h, and 20 °C as the most effective parameters, achieving an 86% reduction in phytic acid, closely matched the model's predictions (R2 = 0.945). This method effectively reduced ANFs, offering a sustainable approach for producing proteins suitable for diverse food products, including plant-based alternatives.
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In the present study, we investigated the effect of sesamin on CYP1A (7-ethoxyresorufin-O-deethylase, EROD) and CYP2E1-like activities (p-nitrophenol hydroxylase, PNPH) in hepatic microsomes obtained from Atlantic salmon (Salmo salar) and common carp (Cyprinus carpio). Addition of sesamin to the incubations in a concentration range from 1 to 200 µM decreased the activities of EROD and PNPH in a concentration dependent manner. It is likely that the inhibition of EROD was mechanism-based as demonstrated by the decrease in the IC50 value from 5.9 to 3.2 µM for A. salmon and from 7.9 to 3.0 µM for common carp when 5 min pre-incubation step was included. Similarly, PNPH activity was inhibited by sesamin with a decrease in the IC50 values from 61.7 to 15.2 µM for A. salmon and from 194.3 to 20.7 µM for common carp. Thus, our results indicated that sesamin can act as a mechanism-based inhibitor of EROD and PNPH activity with similar degree of inhibition in both fish species. More importantly, the inhibition of CYP1A, in addition to being mechanism-based, was competitive with K(i) value of 5.3 µM.
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Antioxidantes/farmacología , Citocromo P-450 CYP1A1/antagonistas & inhibidores , Inhibidores del Citocromo P-450 CYP2E1 , Dioxoles/farmacología , Lignanos/farmacología , Microsomas Hepáticos/química , Animales , Carpas , Concentración 50 Inhibidora , Cinética , SalmónRESUMEN
This review focuses on the expression and regulation of 3ß-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3ß-HSD), with emphasis on the porcine version. 3ß-HSD is often associated with steroidogenesis, but its function in the metabolism of both steroids and xenobiotics is more obscure. Based on currently available literature covering humans, rodents and pigs, this review provides an overview of the present knowledge concerning the regulatory mechanisms for 3ß-HSD at all omic levels. The HSD isoenzymes are essential in steroid hormone metabolism, both in the synthesis and degradation of steroids. They display tissue-specific expression and factors influencing their activity, which therefore indicates their tissue-specific responses. 3ß-HSD is involved in the synthesis of a number of natural steroid hormones, including progesterone and testosterone, and the hepatic degradation of the pheromone androstenone. In general, a number of signaling and regulatory pathways have been demonstrated to influence 3ß-HSD transcription and activity, e.g., JAK-STAT, LH/hCG, ERα, AR, SF-1 and PPARα. The expression and enzymic activity of 3ß-HSD are also influenced by external factors, such as dietary composition. Much of the research conducted on porcine 3ß-HSD is motivated by its importance for the occurrence of the boar taint phenomenon that results from high concentrations of steroids such as androstenone. This topic is also examined in this review.
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17-Hidroxiesteroide Deshidrogenasas/metabolismo , Isomerasas/metabolismo , 17-Hidroxiesteroide Deshidrogenasas/genética , Animales , Hormonas Esteroides Gonadales/metabolismo , Humanos , Isomerasas/genética , PorcinosRESUMEN
The aim of the present review was to assess whether rabbit meat production can help to improve food security in Ukraine and whether it can make a meaningful contribution to the national economy. Rabbit meat is a nutrient-rich and affordable food with a lower environmental impact than red meat from cattle or sheep. Rabbit meat is considered healthy, as it is lower in fat, cholesterol and sodium than other types of meat, and rich in protein. In addition, rabbit meat proteins can serve as a source of bioactive peptides with the angiotensin converting enzyme (ACE) inhibition properties. The health-promoting properties of rabbit meat and role of associated by-products in providing nutritious and safe food for consumers, and in reducing waste in the meat sector, should be promoted. In Ukraine, rabbit meat products are already recommended as part of a healthy diet for children, pregnant women and the elderly, and the market could be broadened by introducing more rabbit-based products for the whole population. Rabbit production in Ukraine is a promising area of economic activity and with a broader market this segment could increase further and become a significant part of the economy. However, the rabbit farming sector in Ukraine needs comprehensive improvement to address existing issues, including the introduction of sustainable production methods in accordance with European animal welfare and meat quality standards.
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Productos de la Carne , Carne , Animales , Femenino , Conejos , Bovinos , Humanos , Ovinos , Embarazo , Ucrania , Carne/análisis , Dieta Saludable , Seguridad AlimentariaRESUMEN
Metabolic transformations of two substrates for human cytochrome P450 (CYP450) 2C9, tolbutamide and diclofenac, were investigated in hepatic microsomes from Atlantic salmon (Salmo salar L.). Tolbutamide hydroxylation followed Michaelis-Menten kinetics. Mean apparent Michaelis-Menten constant (K(m)) and maximum reaction velocity (V(max)) values for 4-hydroxytolbutamide (TBOH) formation were 0.09 ± 0.031 mM and 49.5 ± 6.03 pmol/min/mg, respectively. Addition of sulfaphenazole, an inhibitor for mammalian CYP2C9, in a range from 1 to 200 µM decreased formation of TBOH in a concentration-dependent manner, but not to 50%. Neither fluconazole, an inhibitor of human CYP2C9, nor ketoconazole, inhibitor of CYP1A and CYP3A in fish, affected TBOH formation. In contrast ellipticine, an inhibitor of CYP1A in fish inhibited TBOH formation with the IC(50) value of 12.1 µM. The rate of TBOH formation was competitively inhibited by 100 µM of sesamin in the incubations, but the degree of inhibition did not increase with increased sesamin concentration. Ethoxyresorufin hydroxylase (EROD) activity was inhibited by tolbutamide in a non-competitive manner (inhibition constant K(i) = 218 µM). Our data suggest that tolbutamide is metabolized by salmon microsomes with formation of TBOH. CYP1A might be involved in this reaction as suggested by decreased TBOH formation in the presence of ellipticine and decreased EROD activity in the presence of tolbutamide. Incubation of diclofenac with the microsomes yielded no metabolite formation, suggesting that salmon does not possess diclofenac-metabolizing activity.
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Microsomas Hepáticos/enzimología , Tolbutamida/metabolismo , Animales , Hidrocarburo de Aril Hidroxilasas/antagonistas & inhibidores , Hidrocarburo de Aril Hidroxilasas/metabolismo , Biotransformación , Citocromo P-450 CYP3A/metabolismo , Inhibidores del Citocromo P-450 CYP3A , Diclofenaco/metabolismo , Dioxoles/farmacología , Elipticinas/farmacología , Proteínas de Peces/metabolismo , Fluconazol/farmacología , Hidroxilación , Cetoconazol/farmacología , Cinética , Lignanos/farmacología , Microsomas Hepáticos/efectos de los fármacos , Oxazinas/metabolismo , Salmo salar , Sulfafenazol/farmacología , Tolbutamida/farmacologíaRESUMEN
The present study investigated the effect of surgical (SC) and immunological castration on the steroid metabolizing enzymes 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and sulfotransferase 2A1 (SULT2A1) in male pigs. Thirty-two male pigs were divided in four groups; in one group the pigs were SC before the age of 7 days, two groups were injected with Improvac(®) a vaccine against gonadotropin releasing hormone (immunological castration), while the pigs in the last group remained entire males (EMs). Immunological castration was in one group performed by vaccine injection at ages 11 and 14 weeks, while the other group received injections at ages 17 and 21 weeks. Plasma, adipose and liver tissue were collected at the time of slaughter. Plasma was analyzed for concentrations of testosterone and oestradiol. The adipose tissue was analyzed for the concentration of androstenone, while the liver tissue was analyzed for mRNA and protein expression of 3ß-HSD and SULT2A1. Independent of method, all castrated pigs showed greater mRNA and protein expression of 3ß-HSD and lower levels of all steroids in plasma compared with EMs. Moreover, there was a strong correlation between mRNA and protein expression of 3ß-HSD and steroid levels. The same was not valid for expression of SULT2A1. It is concluded that steroid levels can increase expression of the steroid metabolizing enzyme 3ß-HSD and thereby influence steroid metabolism, e.g. of androstenone.
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17-Hidroxiesteroide Deshidrogenasas/genética , Androsterona/metabolismo , Hígado/enzimología , Sulfotransferasas/genética , 17-Hidroxiesteroide Deshidrogenasas/metabolismo , Tejido Adiposo/metabolismo , Androsterona/sangre , Animales , Estradiol/sangre , Estradiol/metabolismo , Expresión Génica , Masculino , Orquiectomía , Sulfotransferasas/metabolismo , Porcinos , Testosterona/sangre , Testosterona/metabolismoRESUMEN
Recent studies suggest that a diet rich in sugars significantly affects the gut microbiota. Adverse metabolic effects of sugars may partly be mediated by alterations of gut microbiota and gut health parameters, but experimental evidence is lacking. Therefore, we investigated the effects of high intake of fructose or galactose, with/without fructooligosaccharides (FOS), on gut microbiota composition in rats and explored the association between gut microbiota and low-grade systemic inflammation. Sprague-Dawley rats (n = 6/group) were fed the following isocaloric diets for 12 weeks (% of the dry weight of the sugars or FOS): (1) starch (control), (2) fructose (50%), (3) galactose (50%), (4) starch+FOS (15%) (FOS control), (5) fructose (50%)+FOS (15%), (6) galactose (50%)+FOS (15%), and (7) starch+olive (negative control). Microbiota composition in the large intestinal content was determined by sequencing amplicons from the 16S rRNA gene; 341F and 805R primers were used to generate amplicons from the V3 and V4 regions. Actinobacteria, Verrucomicrobia, Tenericutes, and Cyanobacteria composition differed between diets. Bifidobacterium was significantly higher in all diet groups where FOS was included. Modest associations between gut microbiota and metabolic factors as well as with gut permeability markers were observed, but no associations between gut microbiota and inflammation markers were observed. We found no coherent effect of galactose or fructose on gut microbiota composition. Added FOS increased Bifidobacterium but did not mitigate potential adverse metabolic effects induced by the sugars. However, gut microbiota composition was associated with several metabolic factors and gut permeability markers which warrant further investigations.