María Aránzazu Martínez
Complutense University of Madrid
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Featured researches published by María Aránzazu Martínez.
Journal of Agricultural and Food Chemistry | 2008
Arturo Anadón; María Aránzazu Martínez; Marta Martínez; Alba Ríos; Virginia Caballero; Irma Ares; María Rosa Martínez-Larrañaga
Chickens were used to investigate plasma disposition of florfenicol after single intravenous (i.v.) and oral dose (20 mg kg-1 body weight) and to study residue depletion of florfenicol and its major metabolite florfenicol-amine after multiple oral doses (40 mg kg-1 body weight, daily for 3 days). Plasma and tissue samples were analyzed using a high-performance liquid chromatography (HPLC) method. After i.v. and oral administration, plasma concentration-time curves were best described by a two-compartment open model. The mean [ +/- standard deviation (SD)] elimination half-life (t1/2beta) of florfenicol in plasma was 7.90 +/- 0.48 and 8.34 +/- 0.64 h after i.v. and oral administration, respectively. The maximum plasma concentration was 10.23 +/- 1.67 microg mL-1, and the interval from oral administration until maximal concentration was 0.63 +/- 0.07 h. Oral bioavailability was found to be 87 +/- 16%. Florfenicol was converted to florfenicol-amine. After multiple oral dose (40 mg kg-1 body weight, daily for 3 days), in kidney and liver, concentrations of florfenicol (119.34 +/- 31.81 and 817.34 +/- 91.65 microg kg-1, respectively) and florfenicol-amine (60.67 +/- 13.05 and 48.50 +/- 13.07 microg kg-1, respectively) persisted for 7 days. The prolonged presence of residues of florfenicol and florfenicol-amine in edible tissues can play an important role in human food safety, because the compounds could give rise to a possible health risk. A withdrawal time of 6 days was necessary to ensure that the residues of florfenicol were less than the maximal residue limits or tolerance established by the European Union.
Journal of Agricultural and Food Chemistry | 2014
Laura Sánchez-Rivera; Irma Ares; Beatriz Miralles; José Ángel Gómez-Ruiz; Isidra Recio; María Rosa Martínez-Larrañaga; Arturo Anadón; María Aránzazu Martínez
The aim of this study was to investigate the oral bioavailability and kinetics of the milk casein-derived peptide HLPLP, which had previously demonstrated antihypertensive effect in spontaneously hypertensive rats. HLPLP disposition after single intravenous (4 mg/kg body weight) and oral (40 mg/kg body weight) doses was studied in rats. Plasma concentrations of HLPLP [β-casein fragment f(134-138)], and two derived fragments found after HLPLP administration, LPLP [β-casein fragment f(135-138)] and HLPL [β-casein fragment f(134-137)], were determined by ultrahigh performance liquid chromatography (UPLC) coupled on line to a Q-TOF instrument. For HLPLP, the elimination half-lives (T1/2β) were 7.95 min after intravenous and 11.7 min after oral administration. The volume of distribution at steady state (Vss = 30.8 L/kg) suggests a considerable uptake of HLPLP into tissues. HLPLP was converted to the peptides LPLP and HLPL. After HLPLP intravenous administration, the elimination half-lives (T1/2β) for these biotransformed peptides, LPLP and HLPL, were 8.38 and 10.9 min, respectively. After oral administration, HLPLP was rapidly absorbed with an absorption half-life (T1/2a) of 2.79 min. The oral bioavailability of HLPLP was found to be 5.18%. Our study suggested that HLPLP was rapidly absorbed and eliminated after oral administration, biotransformed into smaller fragments LPLP and HLPL, and distributed throughout the body by the circulation blood. The present pharmacokinetic information from a preclinical kinetic study in rats can also play an important role in designing future kinetic studies in humans for assessing HLPLP dose-response relationship.
Expert Opinion on Drug Metabolism & Toxicology | 2014
Arturo Anadón; María Aránzazu Martínez; Victor Castellano; María Rosa Martínez-Larrañaga
Introduction: It is accepted that animal testing should be reduced, refined or replaced as far as it is practicably possible. There are also a wide variety of in vitro models, which are used as screening studies and mechanistic investigations. The ability of an in vitro assay to be reliable, biomedically, is essential in pharmaceutical development. Furthermore, it is necessary that cells used in in vitro testing mimic the phenotype of cells within the human target tissue. Areas covered: The focus of this review article is to identify the key points of in vitro assays. In doing so, the authors take into account the chemical agents that are assessed and the integrated in vitro testing strategies. Expert opinion: There is a transfer of toxicological data from primary in vivo animal studies to in vitro assays. The key element for designing an integrated in vitro testing strategy is summarized as follows: exposure modeling of chemical agents for in vitro testing; data gathering, sharing and read-across for testing a class of chemical; a battery of tests to assemble a broad spectrum of data on different mechanisms of action to predict toxic effects; and applicability of the test and the integrated in vitro testing strategies and flexibility to adjust the integrated in vitro testing strategies to test substance. While these methods will be invaluable if effective, more studies must be done to ensure reliability and suitability of these tests for humans.
Archives of Toxicology | 2016
Xu Wang; Qinghua Wu; Dan Wan; Qianying Liu; Dongmei Chen; Zhenli Liu; María Rosa Martínez-Larrañaga; María Aránzazu Martínez; Arturo Anadón; Zonghui Yuan
Fumonisins (FBs) are widespread Fusarium toxins commonly found as corn contaminants. FBs could cause a variety of diseases in animals and humans, such as hepatotoxic, nephrotoxic, hepatocarcinogenic and cytotoxic effects in mammals. To date, almost no review has addressed the toxicity of FBs in relation to oxidative stress and their metabolism. The focus of this article is primarily intended to summarize the progress in research associated with oxidative stress as a plausible mechanism for FB-induced toxicity as well as the metabolism. The present review showed that studies have been carried out over the last three decades to elucidate the production of reactive oxygen species (ROS) and oxidative stress as a result of FBs treatment and have correlated them with various types of FBs toxicity, indicating that oxidative stress plays critical roles in the toxicity of FBs. The major metabolic pathways of FBs are hydrolysis, acylation and transamination. Ceramide synthase, carboxylesterase FumD and aminotransferase FumI could degrade FB1 and FB2. The cecal microbiota of pigs and alkaline processing such as nixtamalization can also transform FB1 into metabolites. Most of the metabolites of FB1 were less toxic than FB1, except its partial (pHFB1) metabolites. Further understanding of the role of oxidative stress in FB-induced toxicity will throw new light on the use of antioxidants, scavengers of ROS, as well as on the blind spots of metabolism and the metabolizing enzymes of FBs. The present review might contribute to reveal the toxicity of FBs and help to protect against their oxidative damage.
Critical Reviews in Toxicology | 2016
Xu Wang; María Aránzazu Martínez; Qinghua Wu; Irma Ares; María Rosa Martínez-Larrañaga; Arturo Anadón; Zonghui Yuan
Abstract Fipronil (FIP) is widely used across the world as a broad-spectrum phenylpyrazole insecticide and veterinary drug. FIP was the insecticide to act by targeting the γ-aminobutyric acid (GABA) receptor and has favorable selective toxicity towards insects rather than mammals. However, because of accidental exposure, incorrect use of FIP or widespread FIP use leading to the contamination of water and soil, there is increasing evidence that FIP could cause a variety of toxic effects on animals and humans, such as neurotoxic, hepatotoxic, nephrotoxic, reproductive, and cytotoxic effects on vertebrate and invertebrates. In the last decade, oxidative stress has been suggested to be involved in the various toxicities induced by FIP. To date, few reviews have addressed the toxicity of FIP in relation to oxidative stress. The focus of this article is primarily intended to summarize the progress in research associated with oxidative stress as a possible mechanism for FIP-induced toxicity as well as metabolism. The present review reports that studies have been conducted to reveal the generation of reactive oxygen species (ROS) and oxidative stress as a result of FIP treatment and have correlated them with various types of toxicity. Furthermore, the metabolism of FIP was also reviewed, and during this process, various CYP450 enzymes were involved and oxidative stress might occur. The roles of various compounds in protecting against FIP-induced toxicity based on their anti-oxidative effects were also summarized to further understand the role of oxidative stress in FIP-induced toxicity.
Food and Chemical Toxicology | 2012
Arturo Anadón; Felipe Gamboa; María Aránzazu Martínez; Victor Castellano; Marta Martínez; Irma Ares; Eva Ramos; Frank Suárez; María Rosa Martínez-Larrañaga
Chickens were used to investigate plasma disposition of chlortetracycline after single IV (15 mg/kg) and multiple oral administration (60 mg/kg, 5 days) and residue depletion of chlortetracycline after multiple oral doses (60 mg/kg, 5 days). Plasma and tissue samples were analyzed by HPLC. Mean elimination half-lives in plasma were 7.96 and 13.15 h after IV and multiple oral administration. Maximum plasma concentration was 4.33 μg/ml and the interval from oral administration until maximal concentration was 1.79 h. Oral bioavailability was 17.76%. After multiple oral dose, mean kidney, liver and muscle tissue concentrations of chlortetracycline+4-epi-chlortetracycline of 835.3, 192.7, and 126.3 μg/kg, respectively, were measured 1 day after administration of the final dose of chlortetracycline. Chlortetracycline residues were detected in kidney and liver (205.4 and 81.7 μg/kg, respectively), but not in muscle, 3 days after the end of chlortetracycline treatment. The mean chlortetracycline+4-epi-chlortetracycline concentrations were below LOQ at 3 and 5 days after cessation of medication in muscle and liver, respectively. A withdrawal time of 3 days was necessary to ensure that the chlortetracycline residues were less than the maximal residue limits (MRLs) established by the European Union (100, 300, and 600 μg/kg in muscle, liver, and kidney, respectively).
Probiotics, Prebiotics, and Synbiotics#R##N#Bioactive Foods in Health Promotion | 2016
Arturo Anadón; María Rosa Martínez-Larrañaga; Irma Ares; María Aránzazu Martínez
Prebiotics and probiotics must be assessed for health benefits and safety before they can be introduced into the food products. Prebiotics are a selectively fermented ingredient that allows specific changes (composition and/or activity) in the gastrointestinal microflora or microbiota that confers benefits on the well-being and health of the host—particularly increased numbers of lactic acid bacteria and/or bifidobacteria cell counts. The prebiotics and probiotics probably share common mechanisms of action, especially modulation of the endogenous flora, but differ in their composition and metabolism. Probiotics are viable microorganisms, generally bacteria or yeasts, that, when ingested alive in a sufficient amount, have a positive effect on the health going beyond the nutritional ones commonly known. Manipulation of gut flora to enhance its protective and beneficial role represents a promising field of new strategies and tools of inflammatory bowel disease. Many probiotics have a long history of use, but the new emergent probiotics should be of genera and strains commonly found in the healthy human intestinal microflora. When novel microbes and genetically modified organisms are introduced, their efficacy, risk-to-benefit ratio, and safety need to be assessed cautiously. This overview considers the prebiotics and probiotics concept and their uses and mechanisms, the essential endpoints for their evaluation, the main concerns for some of them, and the types of studies to be conducted for efficacy substantiation. Finally, this text describes the regulations and guidances available in the European Union (EU) and in the United States to substantiate a health claim and the qualified perception of safety (QPS) concept introduced a new in the EU framework
Food and Chemical Toxicology | 2013
María Aránzazu Martínez; María Rosa Martínez-Larrañaga; Victor Castellano; Marta Martínez; Irma Ares; Alejandro Romero; Arturo Anadón
Natamycin is a polyene macrolide antibiotic widely used in the food industry as a feed additive to prevent mold contamination of foods. There are many contradictory results on the genotoxic effects of macrolides which could suggest a potential risk for humans. In the present study, the effects of natamycin on the activities of some drug metabolizing enzymes in rat liver microsomes were determined in vivo. Rats were treated orally with natamycin at doses of 0.3, 1, 3 and 10 mg/kg body weight (bw)/day for 6 days. Determinations of cytochrome P450 (CYP) enzyme activities were carried out in hepatic microsomes isolated from rats treated. The activities of CYP2E1, CYP1A1/2 CYP2B1/2 and CYP4A1/2 enzymes significantly decreased after treatment with 1, 3 and 10 mg/kg bw/day, in a dose-dependent manner as compared to control. This effect was not observed after natamycin treatment at dose of 0.3 mg/kg bw/day. Our results suggest that natamycin may not potentiate the toxicity of many xenobiotics via metabolic activation and/or accumulation of reactive metabolites but also might affect the clearance of other xenobiotics detoxified by the studied CYP enzymes.
Nutraceuticals#R##N#Efficacy, Safety and Toxicity | 2016
Arturo Anadón; María Rosa Martínez-Larrañaga; Irma Ares; María Aránzazu Martínez
Prebiotics are of interest because they can reduce the risk of certain conditions and promote better health. In recent years, consumer interest in the relation between diet and health has increased the demand for correct information on prebiotics and has become a growing segment in the world market. This growth has been enhanced by technological innovations, development of new products, and the increasing number of health-conscious consumers interested in products that improve life quality. In this chapter, the Prebiotic concept/prebiotic effects and the sources of dietary oligosaccharides (fructans, nonfructans) are presented, as well as the effects of prebiotics on the gastrointestinal tract, the increase in resistance to GI infections, the mineral homeostasis and nitrogen-containing substrates, and the systemic effects. This chapter also introduces the effects of prebiotics on infants, adults and the elderly, and the use of prebiotics in foods and with medical purposes. Finally, the guidelines of prebiotic safety, and the safety and toxicity considerations are illustrated.
Nutraceuticals#R##N#Efficacy, Safety and Toxicity | 2016
Arturo Anadón; María Rosa Martínez-Larrañaga; Irma Ares; María Aránzazu Martínez
Abstract Interactions between foods, dietary supplements and drugs present complex and challenging problems. They may be caused by either alterations on absorption, distribution, and biotransformation, by excretion of one drug by a food/dietary supplement, or by a combination of their actions and effects. The interactions can have an intense influence on the success of drug treatment and on the adverse effect or side effect profiles of many drugs; however, the interactions are not always harmful to therapy, and in some cases can be used to improve drug absorption or to minimize adverse effects. The different types of drug-nutrients interactions are described in this chapter, as well as the herb-drug interactions of the most important herbal medicines. Finally, food and nutrient-drug interactions are presented. Special mention is made on interactions with grapefruit juice, and mono amine oxidase (MAO) drug inhibitors. Contraindications of herbs during pregnancy are also listed in this chapter.