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1.
Environ Res ; 197: 110991, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33705767

RESUMO

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).

2.
Mol Nutr Food Res ; 65(6): e2001133, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33548087

RESUMO

SCOPE: A high fructose and galactose intake show adverse metabolic effects in animal models and in humans, but it is yet unknown if addition of fermentable dietary fiber can mitigate such effects. This study investigate the effects of high intakes of fructose and galactose, with/without added fructooligosaccharides (FOS), on metabolic factors, inflammation, and gut integrity markers in rats. METHODS AND RESULTS: Rats (n = 6/group) receive different carbohydrates at isocaloric conditions for 12 weeks as follows: 1) starch (control), 2) fructose, 3) galactose, 4) starch + FOS (FOS control), 5) fructose + FOS, and 6) galactose + FOS, together with a high amount of n-6 polyunsaturated fatty acids (n-6 PUFA) in all diets except for in 7) starch + olive oil (negative control). The rats fed the galactose and galactose + FOS diets exhibit lower body weight than other groups. High-galactose diets has more pronounced effects on metabolic factors and gut permeability than high-fructose diets. High-fructose diets show less pronounced effect on these selected markers. No differences in inflammatory markers are detected for any of the diets. CONCLUSIONS: The results suggest potential adverse effects of high galactose and fructose on metabolic factors and gut integrity markers, but not on inflammation. However, several mechanisms are at play, and general net effects are difficult to determine conclusively for the conditions tested.

3.
Toxicol Lett ; 341: 1-10, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33429014

RESUMO

Piscine cytochrome P450 (CYP) enzymes play an important role in the metabolism of xenobiotics. Xenobiotics often act as inducers of CYP1A1 and CYP3A expression and activity in fish. We compared constitutive mRNA expression of CYP1A1, CYP3A27, and CYP3A45 and catalytic activity of CYP1A (7-ethoxyresorufin-O-deethylation, EROD) and CYP3A-like (benzyloxy-4-trifluoromethylcoumarin-O-debenzyloxylation, BFCOD) enzymes in the following six rainbow trout tissues: liver, gill, heart, brain, intestine, and gonad. mRNA expression and activity were present in all investigated tissues. The CYP1A1 mRNA expression was higher in the liver, gill, heart, and brain compared to gonad and intestine. The intestine was the main site of CYP3A27 and CYP3A45 expression. The highest EROD and BFCOD activity was observed in liver tissue followed in descending order by heart, brain, gill, intestine, and gonad. Such differences might be related to the role of CYP physiological functions in the specific tissue. Rainbow trout exposure to 50 mg/kg of ß-naphthoflavone for 48 h resulted in a 7.5- and 5.9-fold increase in liver EROD and BFCOD activity, respectively. In vitro EROD activity inhibition with ellipticine showed tissue-specific inhibition, while ketoconazole decreased BFCOD activity by 50-98 % in all tissues. Further studies are needed to identify all CYP isoforms that are responsible for these activities and modes of regulation.


Assuntos
Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP3A/metabolismo , Regulação Enzimológica da Expressão Gênica/fisiologia , Oncorhynchus mykiss/metabolismo , Animais , Encéfalo/enzimologia , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP3A/genética , Feminino , Brânquias/enzimologia , Intestinos/enzimologia , Fígado/enzimologia , Masculino , Miocárdio/enzimologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Caracteres Sexuais
4.
Animals (Basel) ; 10(10)2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32998259

RESUMO

Surgical castration of piglets without pain relief is still common practice in many countries. Possible alternatives for surgical castration are application of pain relief or anaesthesia or production of boars (entire males) and immunocastrates. Each of these alternatives faces advantages and disadvantages which may result in different citizen attitudes and consumers acceptability. Understanding which practice is acceptable to whom and why may further stimulate implementation. Consumer (n = 3251) and stakeholder (n = 1027) attitudes towards surgical castration without pain relief, surgical castration with anaesthesia, immunocastration, and production of boars were surveyed from April to June 2020 via an online questionnaire in 16 countries (>175 respondents per country). Surgical castration without pain relief was separated from each of the alternatives due to animal welfare and showed the lowest acceptability (32%). Within the alternatives, a further partitioning between the alternatives was based on perceived quality and food safety, with an acceptance of 85% for applying anaesthesia, 71% for immunocastration, and 49% for boar production. Differences depending on professional involvement and familiarity with agriculture could be observed, mainly for the acceptance of surgical castration without anaesthesia, immunocastration, and boars. Castration with anaesthesia was highly accepted by all types of respondents.

5.
Animals (Basel) ; 10(11)2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33114075

RESUMO

This paper reviews the current knowledge on the nutritional requirements of entire male and immunocastrated pigs to obtain an efficient growth, low boar taint level, and good carcass and meat quality. We present the reasons for offering entire males ad libitum access to the diets in order to optimize their protein deposition potential. Boar taint is one of the major issues in the production of entire males; therefore, the impact of various skatole- and indole-reducing feed ingredients is discussed regarding their efficiency and the possible mechanism affecting skatole and indole production in the hindgut. Entire males have lean carcasses, so their intramuscular fat content can be lower than that of surgical castrates or females and the adipose tissue can be highly unsaturated. The possible nutritional strategies to counteract these effects are summarized. We conclude that immunocastrates can be fed similarly to entire males until the second vaccination. However, due to the metabolic changes occurring shortly after the second vaccination, the requirements for essential amino acids are markedly lower in immunocastrates than in entire males.

6.
Molecules ; 25(11)2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32531944

RESUMO

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.

7.
J Agric Food Chem ; 68(23): 6333-6346, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32432868

RESUMO

Meat-diet-induced changes in gut microbiota are often accompanied with the development of various metabolic and inflammatory disorders. The exact biochemical mechanism underlying these effects is not well elucidated. This study aims to evaluate how meat proteins in high-fat diets affect tryptophan metabolism in rats. The high-chicken-protein (HFHCH) or high-pork-protein (HFHP) diets increased levels of skatole and indole in cecal and colonic contents, feces, and subcutaneous adipose tissue. The HFHCH and HFHP diets also increased the abundance of Lactobacillus, the Family XIII AD3011 group, and Desulfovibrio in the cecum and colon, which may be involved in the production of skatole and indole. Additionally, high-meat-protein diets induced lower activity of skatole- and indole-metabolizing enzyme CYP2E1 in liver compared with low-meat-protein diets. This work highlights the negative impact of high meat proteins on physiological responses by inducing dysbiosis of gut microbiota and tryptophan metabolism.

8.
J Food Sci Technol ; 57(2): 595-605, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32116369

RESUMO

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.

9.
Chemosphere ; 238: 124538, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31454745

RESUMO

Although banned, dyes, such as Victoria pure blue BO (VPBO), are illicitly used in aquaculture to treat or prevent infections due to their therapeutic activities. The present study examined the formation of phase I and phase II metabolites derived from VPBO using trout liver microsomes and S9 proteins. The well-known malachite green (MG) dye was also studied as a positive control and to compare its metabolism with that of VPBO. First, we optimised the incubation conditions for the detection of VPBO and MG metabolites by studying the formation of cytochrome P450 (CYP) substrates. Using the determined conditions (2 h at 20 °C), we incubated VPBO with trout microsomal and S9 fractions induced with ß-naphtoflavone, and analysed the supernatant in a LC-LTQ-Orbitrap-HRMS system. The in vitro assays led to the detection of 16 VPBO metabolites from Phase I reactions, arising in particular from reactions with CYP1A. No metabolites were detected from Phase II reactions. The main metabolite detected, deethyl-VPBO, was CID-fragmented to determine its chemical structure, and thus recommend a potential biomarker for the control of VPBO in farmed fish foodstuffs.


Assuntos
Corantes/metabolismo , Peixes/metabolismo , Contaminação de Alimentos/análise , Compostos de Amônio Quaternário/metabolismo , Alimentos Marinhos , Animais , Aquicultura , Sistema Enzimático do Citocromo P-450/metabolismo , Metabolômica , Microssomos Hepáticos/metabolismo
10.
Clin Nutr ; 39(1): 159-165, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30685298

RESUMO

BACKGROUND & AIMS: Rye consumption has shown beneficial effects on prostate cancer tumors, as indicated by slower initial tumor growth in animal models and lowering of prostate-specific antigen (PSA) in humans. This study evaluated the effects of whole grain/bran rye consumption on low-grade inflammation and endothelial function biomarkers in men with prostate cancer. METHODS: Seventeen men with untreated, low-grade prostate cancer consumed 485 g rye whole grain and bran products (RP) per day or refined wheat products with added cellulose (WP) in a randomized crossover design. Fasting blood samples were taken before and after 2, 4, and 6 weeks of treatment. RESULTS: Concentrations of tumor nuclear factor-receptor 2 (TNF-R2), e-selectin, and endostatin were significantly lower after consumption of the RP diet compared with WP (p < 0.05). Cathepsin S concentration was positively correlated to TNF-R2 and endostatin concentrations across all occasions. Strong correlations were consistently found between intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and between interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA). No effect of intervention was found in 92 inflammation-related protein biomarkers measured in a proximity extension assay. CONCLUSIONS: RP diet lowered TNF-R2, e-selectin, and endostatin, compared with WP in men with prostate cancer. These effects were accompanied by a reduction in PSA.

11.
Toxicol Lett ; 303: 67-71, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30599194

RESUMO

The hepatic cytochrome p450 enzymes 1 A, 2A19 and 2E1 is very important for the elimination of skatole from the body of pigs. Impaired skatole metabolism, results in skatole accumulation, which give rise to off flavor of the meat. Several metabolites of skatole has been identified, however the role of these metabolites in the inhibition of the skatole metabolizing enzymes are not documented. Using microsomes from pigs and fish, we determined the ability of several skatole metabolites to inhibit CYP1 A, CYP2A19 and CYP2E1 dependent activity. Our results show that 2-aminoacetophenone is an inhibitor of porcine CYP2A19 and CYP2E1 activity, but not the piscine orthologues. In conclusion, there is species specific differences in the inhibition of CYP1 A and CYP2A19 dependent metabolism of probe substrates. This is relevant to the evaluation of different model systems and to the reduction of off flavor of meat.


Assuntos
Inibidores do Citocromo P-450 CYP2E1/toxicidade , Fígado/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Escatol/toxicidade , Acetofenonas/toxicidade , Animais , Cumarínicos/toxicidade , Citocromo P-450 CYP1A1/antagonistas & inibidores , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Peixes , Fígado/metabolismo , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Nitrofenóis/toxicidade , Oxazinas/toxicidade , Carne Vermelha/análise , Alimentos Marinhos/análise , Especificidade da Espécie , Suínos
12.
Basic Clin Pharmacol Toxicol ; 124(1): 32-39, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30171805

RESUMO

Cytochrome P450 (CYP) is a major group of enzymes, which conduct Phase I metabolism. Among commonly used animal models, the pig has been suggested as the most suitable model for investigating drug metabolism in human beings. Moreover, porcine CYP2A19 and CYP2E1 are responsible for the biotransformation of both endogenous and exogenous compounds such as 3-methylindole (skatole), sex hormones and food compounds. However, little is known about the regulation of porcine CYP2A19 and CYP2E1. In this MiniReview, we summarise the current knowledge about the regulation of porcine CYP2A19 and CYP2E1 by environmental, biological and dietary factors. Finally, we reflect on the need for further research, to clarify the interaction between active feed components and the porcine CYP system.


Assuntos
Ração Animal , Citocromo P-450 CYP2A6/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Escatol/metabolismo , Suínos/metabolismo , Animais , Biotransformação , Citocromo P-450 CYP2A6/genética , Citocromo P-450 CYP2E1/genética , Hormônios Esteroides Gonadais/metabolismo , Humanos , Homologia de Sequência , Xenobióticos/metabolismo
13.
Environ Toxicol Pharmacol ; 62: 199-202, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30077163

RESUMO

Naturally- and anthropogenically-produced cresols could pose serious risks to fish health. In this study, three piscine CYP isoforms were investigated for their abilities to interact with p-cresol. Therefore, the activity of 7-ethoxyresorufin-O-deethylase (EROD), 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase (BFCOD), and p-nitrophenol hydroxylase (PNPH) were evaluated in the hepatic microsomes of juvenile rainbow trout. Results showed that EROD activity was inhibited in a competitive manner, BFCOD activity was inhibited in presence the highest tested p-cresol concentration and PNPH activity was not affected. These results indicate that p-cresol might affect the ability of fish to metabolize numerous aromatic hydrocarbons and dioxin compounds, which are present in the aquatic environment.


Assuntos
Cresóis/toxicidade , Citocromo P-450 CYP1A1/antagonistas & inibidores , Proteínas de Peixes/metabolismo , Oncorhynchus mykiss/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Citocromo P-450 CYP1A1/metabolismo
14.
Ecotoxicol Environ Saf ; 164: 92-99, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30098510

RESUMO

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.


Assuntos
Cyprinidae , Monitoramento Ambiental , Rios/química , Poluentes Químicos da Água/análise , Animais , Biomarcadores/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , República Tcheca , DDT/análise , Poluição Ambiental , Peixes/metabolismo , Hidrocarbonetos Clorados/análise , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Bifenilos Policlorados/análise , Análise de Componente Principal , Vitelogeninas/sangue , Qualidade da Água
15.
Sci Total Environ ; 625: 1494-1509, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29996446

RESUMO

Concerns about the effect of sewage treatment plant (STP) effluent on the health of freshwater ecosystems have increased. In this study, a unique approach was designed to show the effect of an STP effluent-dominated stream on native wild brown trout (Salmo trutta L.) exposed under fully natural conditions. Zivny stream is located in South Bohemia, Czech Republic. The downstream site of Zivny stream is an STP-affected site, which receives 25% of its water from Prachatice STP effluent. Upstream, however, is a minimally polluted water site and it is considered to be the control site. Native fish were collected from the upstream site, tagged, and distributed to both upstream and downstream sites. After 30, 90, and 180days, fish were recaptured from both sites to determine whether the downstream site of the Zivny stream is associated with the effects of environmental pollution. Several biomarkers indicating the oxidative stress and antioxidant enzyme activities, cytochrome P450 activity, xenoestrogenic effects, bacterial composition, and lipid composition were investigated. Additionally, polar chemical contaminants (pharmaceuticals and personal care products (PPCPs)) were quantified using polar organic chemical integrative samplers (POCIS). Fifty-three PPCPs were detected in the downstream site; 36 of those were constantly present during the 180-day investigation period. Elevated hepatic 7-benzyloxy-4-trifluoromethylcoumarin-O-debenzyloxylase (BFCOD) (after 90days) and blood plasma vitellogenin concentrations in males were detected in fish downstream of the STP effluent during all sampling events. An increase in the fishes' total fat content was also observed, but with low levels of ω-3 fatty acid in muscle tissue. Two bacterial taxa related to activated sludge were found in the intestines of fish from downstream. Our results show that Prachatice STP is a major source of PPCPs in the Zivny stream, which has biological consequences on fish physiology.


Assuntos
Monitoramento Ambiental , Microbioma Gastrointestinal/fisiologia , Truta/fisiologia , Eliminação de Resíduos Líquidos , Poluentes da Água/toxicidade , Animais , Biomarcadores/metabolismo , República Tcheca , Ecossistema , Feminino , Masculino , Rios/química , Esgotos , Truta/microbiologia , Vitelogeninas/metabolismo
16.
Sci Total Environ ; 635: 1160-1169, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29710571

RESUMO

Sewage treatment plants (STPs) are one of the major source of pharmaceuticals and personal care products in the aquatic environment. Generally, the effects of individual chemicals on fish are studied under laboratory conditions, which leads to results that are potentially not realistic regarding the effects of these chemicals under environmental conditions. Therefore, in this study, common carps were held in exposed pond that receive water from STP effluents for 360 days under natural conditions. Elimination of xenobiotics starts in the fish intestine, in which the microbial community strongly influences its function. Moreover, the fish intestine functions as crucial organ for absorbing lipids and fatty acids (FA), with consequent transport to the liver where their metabolism occurs. The liver is the primary organ performing xenobiotic metabolism in fish, and therefore, the presence of pollutants may interact with the metabolism of FA. The catalytic activity of CYP1A and CYP3A-like enzymes, their gene expression, FA composition and intestinal microbiome consortia were measured. The catalytic activity of enzymes and their gene and protein expression, were induced in hepatic and intestinal tissues of fish from the exposed pond. Also, fish from the exposed pond had different compositions of FA than those from the control pond: concentration of 18:1 n-9 and 18:2 n-6 were significantly elevated and the longer chain n-3 FA 20:5 n-3, 22:5 n-3 and 22:6 n-3 were significantly lowered. There were clear differences among microbiome consortia in fish intestines across control and exposed groups. Microbiome taxa measured in exposed fish were also associated with those found in STP activated sludge. This study reveals that treated STP water, which is assumed to be clean, affected measured biomarkers in common carp.


Assuntos
Carpas/fisiologia , Eliminação de Resíduos Líquidos , Águas Residuárias/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/metabolismo , Fígado/metabolismo , Esgotos , Poluentes Químicos da Água/análise
17.
Food Chem ; 258: 245-253, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-29655729

RESUMO

The physiological effects of the Stevia-derived compounds, rebaudioside A, stevioside and steviol have been the focus of several studies due to their use as sweeteners in food. Despite that, little is known about their potential food-drug interactions. In the present study, IPEC-J2 cells and primary hepatocytes were used to investigate the effect of rebaudioside A, stevioside and steviol on cytochrome p450 (CYP) mRNA expression. Moreover, hepatic microsomes were used to investigate direct interactions between the compounds and specific CYP activity. In IPEC-J2 no changes in mRNA expression of CYP1A1 or CYP3A29 were observed with the Stevia-derived compounds. In primary hepatocytes all three tested compounds induced a significant increase in CYP3A29 expression. The tested compounds had no direct effect on specific CYP activity. In conclusion, rebaudioside A, stevioside and steviol induce only minor or no changes to the CYP expression and activity, and are not likely to cause food-drug interactions.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Diterpenos de Caurano/química , Diterpenos de Caurano/farmacologia , Glucosídeos/farmacologia , Transcriptoma/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP1A1/química , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Glucosídeos/química , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Ocludina/genética , Ocludina/metabolismo , Suínos
18.
Chemosphere ; 205: 380-386, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29704845

RESUMO

This study examined the ability of several human pharmaceuticals to modulate hepatic piscine CYP-mediated monooxygenase activities. Effects of six pharmaceuticals: diclofenac, sulfamethoxazole, tramadol, carbamazepine, venlafaxine and nefazodone, were investigated in vitro in rainbow trout hepatic microsomes. The reactions of 7-ethoxyresorufin-O-deethylase (EROD) and benzyloxy-4-trifluoromethylcoumarin-O-debenzyloxylase (BFCOD), were used as markers for hepatic CYP1A and CYP3A-like activities, respectively. Our results showed that EROD and BFCOD activities were both affected by nefazodone. Nefazodone inhibited EROD in a dose dependent manner and was found to be a potent non-competitive inhibitor of EROD with a Ki value of 6.6 µM. BFCOD activity was inhibited non-competitively in the presence of nefazadone with Ki value of 30.7 µM. BFCOD activity was slightly reduced only by the highest concentration of carbamazepine. Diclofenac, sulfamethoxazole, tramadol, and venlafaxine did not affect the activity of either EROD or BFCOD. We further exposed microsomal fraction to mixtures of six pharmaceuticals to investigate potential inhibition. The results showed that EROD and BFCOD activity was inhibited on 94% and 80%, respectively at higher tested concentration. To our knowledge, this is the first report to demonstrate an inhibitory effect of nefazodone on hepatic CYP1A and CYP3A-like proteins in rainbow trout.


Assuntos
Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP3A/metabolismo , Microssomos Hepáticos/metabolismo , Oncorhynchus mykiss/metabolismo , Animais , Humanos , Fígado/metabolismo , Microssomos Hepáticos/enzimologia , Preparações Farmacêuticas/metabolismo , Piperazinas , Triazóis/farmacologia , Poluentes Químicos da Água
19.
Food Chem Toxicol ; 113: 14-18, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29353070

RESUMO

Warfarin is a commonly used anticoagulant drug and is a derivate of coumarin. Cytochrome P450 2C9 (CYP2C9) plays the key role in transformation of coumarin and thus, influences determination of warfarin dosage. A number of factors including dietary compounds such as sesamin, caffeic acid and ferulic acids can regulate the activity of CYP2C9. The present study tested the hypothesis that sesamin, episesamin, caffeic acid and ferulic acid decreases the rate of warfarin 7-hydroxylation via inhibition of hepatic CYP2C9. The experiments were conducted on hepatic microsomes from human donors. It was demonstrated that the rate of 7-hydroxylation of warfarin was significantly decreased in the presence of sesamin in the range of concentrations from 5 to 500 nM, and was not affected by episesamin, caffeic acid and ferulic acid in the same range of concentrations. The kinetic analysis indicated non-competitive type of inhibition by sesamin with Ki = 202 ±â€¯18 nM. In conclusion, the results of our in vitro study revealed that sesamin was able to inhibit formation of a major metabolite of warfarin, 7-hydroxywarfarin. The potentially negative consequences of the consumption of high amounts of sesamin-containing food or dietary supplements in warfarin-treated patients need to be further studied.


Assuntos
Anticoagulantes/metabolismo , Ácidos Cafeicos/farmacologia , Ácidos Cumáricos/farmacologia , Dioxóis/farmacologia , Lignanas/farmacologia , Microssomos Hepáticos/metabolismo , Varfarina/metabolismo , Suplementos Nutricionais , Dioxóis/química , Feminino , Alimentos , Humanos , Hidroxilação , Concentração Inibidora 50 , Cinética , Lignanas/química , Masculino
20.
Xenobiotica ; 48(3): 232-240, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28316274

RESUMO

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.


Assuntos
Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP3A/metabolismo , Indóis/farmacologia , Estilbenos/farmacologia , Animais , Citocromo P-450 CYP1A1/antagonistas & inibidores , Citocromo P-450 CYP3A/genética , Inibidores do Citocromo P-450 CYP3A/farmacologia , Interações Alimento-Droga , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Receptor de Pregnano X , Receptores de Hidrocarboneto Arílico/genética , Receptores de Esteroides/genética , Resveratrol , Suínos
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