Bifurcaria bifurcata extract exerts antioxidant effects on human Caco-2 cells

The present research study investigated the potential protective effect of Bifurcaria bifurcata extract on cell viability and antioxidant defences of cultured human Caco-2 cells submitted to oxidative stress induced by tert-butylhydroperoxide (tert-BOOH). Aqueous extracts were firstly characterized in terms of total phenolic contents. Concentrations of reduced glutathione (GSH) and malondialdehyde (MDA), generation of reactive oxygen species (ROS), nitric oxide (NO) production, antioxidant enzymes activities [NADPH quinone dehydrogenase 1 (NQO1) and glutathione S-transferase (GST)], caspase 3/7 activity and gene expression linked to apoptosis, proinflammation and oxidative stress signaling pathways were used as markers of cellular oxidative status. B. bifurcata extract prevented the cytotoxicity, the decrease of GSH, the increase of MDA levels and the ROS generation induced by tert-BOOH. B. bifurcata extract prevented the significant decrease of NQO1 and GST activities, and the significant increase of caspase 3/7 activity induced by tert-BOOH. B. bifurcata extract also caused an over-expression of GSTM2, Nrf2 and AKT1 transcriptors, as well as reduced ERK1, JNK1, Bax, BNIP3, NFκB1, IL-6 and HO-1 gene expressions induced by tert-BOOH suggesting an increase in cellular resistance against oxidative stress. The results of the biomarkers analyzed show that treatment of Caco-2 cells with B. bifurcata extract enhance antioxidant defences, which imply an improved cell response to an oxidative challenge. B. bifurcata extract possesses strong antioxidant properties and may be a potential effective alternative to oxidant agents in the functional food industry.This work was supported by the Project Ref. PID 2020-15979RR-C33 from the Ministerio de Ciencia e Innovación, Spain.Peer reviewe

Report of the Scientific Committee of the Spanish Agency for Food Safety and Nutrition (AESAN) in relation to the effect on the Spanish population of the derogation of national regulation on maximum allowed limits for aflatoxins B1, B2, G1 and G2 in food

Las aflatoxinas son metabolitos tóxicos producidos por varias especies de hongos del género Aspergillus que crecen en plantas y alimentos de origen vegetal. De entre todas ellas (B1, B2, G1, G2, M1 y M2), destaca desde el punto de vista de la seguridad alimentaria la aflatoxina B1, tanto por ser la más prevalente en alimentos como la más tóxica para los seres humanos. La Unión Europea, debido a la toxicidad de estos compuestos y con el fin de garantizar una protección eficaz de la salud pública, ha establecido mediante el Reglamento (CE) Nº 1881/2006 contenidos máximos para la aflatoxina B1 y la suma de aflatoxinas B1, B2, G1 y G2 en diversos alimentos, entre los que se incluyen aquellos en los cuales la contaminación por este tipo de toxinas resulta más frecuente y puede resultar más peligrosa para la salud humana. En España, previamente a lo establecido por el Reglamento (CE) Nº 1881/2006, ya se dispone de una norma reguladora, el Real Decreto 475/1988, en el cual se establecen límites máximos permitidos de aflatoxinas B1, B2, G1 y G2 en alimentos para consumo humano de 10 μg/kg para la suma de dichas aflatoxinas y de 5 μg/kg para la aflatoxina B1. Si bien es cierto que el Reglamento (CE) Nº 1881/2006 cubre los alimentos que de manera más habitual pueden representar un riesgo para la salud humana originado por la presencia de aflatoxinas, existen trabajos científicos en los cuales se ha demostrado la presencia tanto de aflatoxinas totales como de aflatoxina B1 en alimentos no incluídos en el Reglamento (CE) Nº 1881/2006 en cantidades superiores a las establecidas como límites en el Real Decreto 475/1988. Por este motivo, y sin perjuicio de las medidas de gestión que sean pertinentes, el Comité Científico considera que, en este momento y hasta que se disponga de datos representativos de la presencia de aflatoxinas en algunos alimentos no incluídos en la legislación europea tales como la chufa, el Real Decreto 475/1988 que regula los límites máximos permitidos de aflatoxinas B1, B2, G1 y G2 ofrece un nivel de protección significativo para el consumidor respecto a determinados alimentos no regulados por el Reglamento (CE) Nº 1881/2006.Aflatoxins are toxic metabolites produced by some species of molds belonging to the genus Aspergillus which grow on plants and vegetable-origin foods. Among the aflatoxins that can be found (B1, B2, G1, G2, M1 and M2), from a food safety point of view the most remarkable is aflatoxin B1, because it is the most prevalent in foods and toxic for humans. Due to the toxicity of these substances and to protect consumers’ health, the European Union has stated maximum residue limits (MRL) for aflatoxins in foods, in the Commission Regulations (EC) No 1881/2006. MRL have been established for aflatoxin B1 and the sum of B1, B2, G1 and G2 in different foods, including those in which contamination with these kind of toxins is more frequent and can be more dangerous for human health. The Spanish Royal Decree 475/1988, approved before the Commission Regulation (EC) No 1881/ 2006, sets MRL for the aflatoxins in food for human consumption; 5 μg/kg for aflatoxin B1 and 10 μg/ kg for the sum of aflatoxin B1, B2, G1 and G2. Despite the Commission Regulation (EC) No 1881/2006 includes food which most could usually pose a risk for human health, specific papers have demonstrated the presence of total aflatoxins and aflatoxin B1 in foods not included in the Commission Regulation (EC) No 1881/2006, even at higher concentrations than those set up by the Spanish Royal Decree 475/1988. For this reason, notwithstanding the management measures that are pertinent, the scientific committee considers that, while there are no more data about maximum limits for these substances other food samples different than those included in the previously mentioned legislations (as tiger nuts or other doubtful foods regarding their producing conditions) the Royal Decree 475/1988 offers a significant protection for consumers

Clasificación toxicológica, envasado y etiquetado de productos químicos.

Las Organizaciones Internacionales han desarrollado\ud a lo largo de los años normas legales, reglamentarias y administrativas\ud relativas al uso de sustancias peligrosas que permiten la\ud transmisión de la información de prevención y control, mediante\ud etiquetas o fichas de datos de seguridad, a los usuarios de\ud dichos productos químicos. A este respecto, la Unión Europea\ud ha introducido legislación específica diseñada para proteger la\ud salud humana y el medio ambiente. Una correcta clasificación,\ud envasado y etiquetado de los productos químicos es fundamental\ud para identificar los peligros derivados de sus usos. La etiqueta\ud es, a menudo, la única información de los peligros de la\ud que disponen tanto los usuarios como los trabajadores. En materia\ud de sustancias y preparados peligrosos existe legislación europea\ud desde 1967, fecha en que se reconoció que las disposiciones\ud nacionales sobre clasificación, envasado y etiquetado de productos\ud químicos (fundamentalmente productos industriales peligrosos)\ud debían de armonizarse en el seno de la Unión Europea\ud para la prevención y control de los riesgos derivados, y para eliminar\ud las barreras comerciales que podían suponer las disposiciones\ud nacionales en los Estados miembros. El objetivo de este\ud trabajo es presentar una revisión de toda la legislación en la\ud Unión Europea sobre clasificación, envasado y etiquetado de\ud productos químicos y los principios de su evaluación del riesg

Oral Bioavailability and Plasma Disposition of Pefloxacin in Healthy Broiler Chickens

Informe Descriptivo Profesional (Ingeniero Mecánico Eléctrico)--Universidad de Piura. Facultad de Ingeniería. Programa Académico de Ingeniería Mecánico Eléctrica, 2009.Este informe descriptivo da a conocer la forma de administrar un proyecto de instalaciones eléctricas desde su desarrollo hasta su ejecución y las actividades de supervisión que se desarrollan, así como los parámetros y cálculos bajo los que se evalúan

Oral Bioavailability and Plasma Disposition of Pefloxacin in Healthy Broiler Chickens

The pharmacokinetics of pefloxacin after single 10 mg/kg BW intravenous (IV) and oral doses were studied in healthy broiler chickens. For 24 h, serial blood samples were obtained after IV and oral administration. Concentrations of pefloxacin and its major metabolite N-demethyl pefloxacin (norfloxacin) were measured by use of high-performance liquid chromatography. The plasma concentrations–time data were found to fit a two-compartment open model. For pefloxacin, the elimination half-life (t½β) was 8.44 ± 0.48 and 13.18 ± 0.82 h after IV and oral administration, respectively. After single oral dose, pefloxacin was rapidly absorbed with an absorption half-life (t½a) and TMAX of 0.87 ± 0.07 and 2.01 ± 0.12 h, respectively. Maximum plasma concentration (CMAX) was 4.02 ± 0.31 µg/mL. Oral bioavailability of pefloxacin was found to be 70 ± 2%. Pefloxacin was converted to N-demethyl pefloxacin (norfloxacin). This metabolite represented 5% of the parent drug plasma concentrations. The maximal plasma concentration (CMAX) of N-demethyl pefloxacin (norfloxacin) was calculated as 0.19 ± 0.01 mg/mL. The t½β of N-demethyl pefloxacin after oral pefloxacin administration was 10.93 ± 0.80 h. The results indicate that an oral dose of 10 mg pefloxacin/kg BW, every 24 h, should be effective in treatment of the most systemic infections in poultry

Fipronil induces CYP isoforms in rats

The goal of the present study was to evaluate fipronil effects on the activities of drug metabolizing enzymes in rat liver microsomes. Rats were orally treated with fipronil at doses of 1, 5, 10 and 15 mg/kg bw/day for 6 days. Determinations of cytochrome P450 (CYP) enzyme activities were carried out in hepatic microsomes isolated from treated rats. The activities of some members of CYP2E, CYP1A, CYP2A, CYP2B and CYP3A subfamilies significantly increased after fipronil treatment in a dose-dependent manner as compared to control. The major effects were observed in the O-deethylation of ethoxyresorufin and O-demethylation of methoxyresorufin (reflecting CYP1A1/2 activities), in the O-depenthylation of pentoxyresorufin and 16β-hydroxylation of testosterone (reflecting CYP2B1/2 activities), and in the N-demethylation of erythromycin and 6β-hydroxylation of testosterone (reflecting CYP3A1/2 activities). Immunoblot studies revealed that fipronil increased the apoprotein levels of CYP1A1. Our results suggest that fipronil is an inducer of hepatic phase I CYP enzymes, causing an increased potential to interact with a wide range of xenobiotics or endogenous chemicals that are substrates of the CYP1A, CYP2B and CYP3A subfamilies. Further investigations are required to in vivo evaluate the potential of the metabolite fipronil sulfone as an inducer of phase I CYP enzymesUniversidad Complutense de Madrid (UCM-BSGH/GR3/14)Comunidad de Madrid (S2013/ABI-2728)Depto. de Farmacología y ToxicologíaFac. de VeterinariaTRUEpu

Oxidative stress and related gene expression effects of cyfluthrin in human neuroblastoma SH-SY5Y cells: Protective effect of melatonin

This study was designed to assess oxidative stress induction in human neuroblastoma SH-SY5Y cells in response to cyfluthrin exposure. Cell viability MTT assay was carried out to assess cyfluthrin cytotoxicity; IC30 and IC50 values for cyfluthrin were calculated to be 4.81 ± 0.92 μM and 19.39 ± 3.44 μM, respectively. Cyfluthrin induced a significant increase in ROS generation, lipid peroxides measured as malondialdehyde (MDA) and nitric oxide (NO) production and a significant decrease in NQO1 activity. The antioxidant activity of melatonin (MEL), Trolox, N-acetylcysteine (NAC) and Sylibin against cyfluthrin-induced oxidative stress was examined. Cyfluthrin increased significantly gene expressions of apoptosis, proinflammation and oxidative stress (Bax, Bcl-2, Casp-3, BNIP3, AKT1, p53, APAF1, NFκB1, TNFα and Nrf2) mediators. In the most genes, the mRNA levels induced by cyfluthrin were partially reduced by MEL (1 μM). Cyfluthrin effects on gene expression profiling of oxidative stress pathway by Real-Time PCR array analysis showed that of the 84 genes examined, (fold change > 1.5) changes in mRNA levels were detected in 31 genes: 13 upregulated and 18 down-regulated. A fold change>3.0 fold was observed on upregulated CYBB, DUOX1, DUOX2, AOX1, BNIP3, HSPA1A, NOS2, and NQO1 genes. The greater fold change reversion (2.5 fold) by MEL (1 μM) was observed on cyfluthrin-upregulated CYBB, AOX1, BNIP3 and NOS2 genes. These results demonstrated that oxidative stress is a key element in cyfluthrin induced neurotoxicity as well as MEL may play a role in reducing cyfluthrin-induced oxidative stress.Ministerio de Economía, Industria y CompetitividadDepto. de Farmacología y ToxicologíaFac. de VeterinariaTRUEpu

Protective effects of culture extracts (CB08035-SCA and CB08035-SYP) from Marinobacter hydrocarbonoclasticus (strain CB08035) against oxidant-induced stress in human colon carcinoma Caco-2 cells

The present study investigated the effect of culture extracts (CB08035-SCA and CB08035-SYP) from Marinobacter hydrocarbonoclasticus (strain CB08035) on cell viability and the potential protective effects attributed to molecular mechanisms underlying antioxidant response to survive oxidative stress injuries. Caco-2 cells were submitted to oxidative stress by treatment with tert-butyl hydroperoxide (t-BOOH). Both extracts prevented cell damage and enhanced activity of antioxidant defenses (NQO1 and GST activities and GSH levels) reduced by treatment with t-BOOH. Increased ROS and caspase 3/7 activity induced by t-BOOH were dose-dependently prevented when cells were treated with the extracts. CB08035-SCA caused up-regulation of Nrf2, AKT1 and Bcl-2 gene expressions. Moreover, CB08035-SCA and CB08035-SYP treatments reduced significantly Bax, BNIP3, APAF1, ERK1, JNK1, MAPK1, NFκB1, TNFα, IL-6, IL-1β and HO-1 gene expressions of apoptosis, proinflammation and oxidative stress induced by t-BOOH. CB08035-SCA and CB08035-SYP CPE extracts confer a significant protection against oxidative insults to cells. Our results show that culture extracts CB08035-SCA and CB08035-SYP from M. hydrocarbonoclasticus (strain CB08035) appeared to have antioxidant potential, based on their ability to protect antioxidant enzymes and mRNA gene expressions linked to apoptosis/oxidative pathways. These results suggest that culture extracts CB08035-SCA and CB08035-SYP can be a potential ingredient in the pharmaceutical and cosmeceutical industries.This work was supported by the Project Ref. RTA2015-00010-C03(02-03) from the Ministerio de Economía, Industria y Competitividad, Spain.Peer reviewe

Oxidative stress and metabolism: A mechanistic insight for glyphosate toxicology

Glyphosate (GLYP) is a widely used pesticide; it is considered to be a safe herbicide for animals and humans because it targets 5-enolpyruvylshikimate-3-phosphate synthase. However, there has been increasing evidence that GLYP causes varying degrees of toxicity. Moreover, oxidative stress and metabolism are highly correlated with toxicity. This review provides a comprehensive introduction to the toxicity of GLYP and, for the first time, systematically summarizes the toxicity mechanism of GLYP from the perspective of oxidative stress, including GLYP-mediated oxidative damage, changes in antioxidant status, altered signaling pathways, and the regulation of oxidative stress by exogenous substances. In addition, the metabolism of GLYP is discussed, including metabolites,metabolic pathways, metabolic enzymes, and the toxicity of metabolites. This review provides new ideas for the toxicity mechanism of GLYP and proposes effective strategies for reducing its toxicity.Depto. de Farmacología y ToxicologíaFac. de VeterinariaTRUEpu