Person: Martínez Caballero, María Aranzazu
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First Name
María Aranzazu
Last Name
Martínez Caballero
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Veterinaria
Department
Farmacología y Toxicología
Area
Toxicología
Identifiers
4 results
Search Results
Now showing 1 - 4 of 4
Item Pyrethroid insecticide lambda-cyhalothrin induces hepatic cytochrome P450 enzymes, oxidative stress and apoptosis in rats(Science of the Total Environment, 2018) Martínez Caballero, María Aranzazu; Ares Lombán, Irma; Rodríguez, Jose Luis; Martínez Caballero, Marta; Roura-Martínez, David; Castellano Santos, Víctor Jesús; López Torres, Bernardo; Martínez Larrañaga, María Rosa; Anadón Navarro, Arturo RamónThis study aimed to examine in rats the effects of the Type II pyrethroid lambda-cyhalothrin on hepatic microsomal cytochrome P450 (CYP) isoform activities, oxidative stress markers, gene expression of proinflammatory, oxidative stress and apoptosis mediators, and CYP isoform gene expression and metabolism phase I enzyme PCR array analysis. Lambda-cyhalothrin, at oral doses of 1, 2, 4 and 8 mg/kg bw for 6 days, increased, in a dose-dependent manner, hepatic activities of ethoxyresorufin O-deethylase (CYP1A1), methoxyresorufin O-demethylase (CYP1A2), pentoxyresorufin O-depentylase (CYP2B1/2), testosterone 7α- (CYP2A1), 16β-(CYP2B1), and 6β-hydroxylase (CYP3A1/2), and lauric acid 11- and 12-hydroxylase (CYP4A1/2). Similarly, lambda-cyhalothrin (4 and 8 mg/kg bw, for 6 days), in a dose-dependent manner, increased significantly hepatic CYP1A1, 1A2, 2A1, 2B1, 2B2, 2E1, 3A1, 3A2 and 4A1 mRNA levels and IL-1β, NFκB, Nrf2, p53, caspase-3 and Bax gene expressions. PCR array analysis showed from 84 genes examined (P b 0.05; fold change N 1.5), changes in mRNA levels in 18 genes: 13 up-regulated and 5 down-regulated. A greater fold change reversion than 3-fold was observed on the up-regulated ALDH1A1, CYP2B2, CYP2C80 and CYP2D4 genes. Ingenuity Pathway Analysis (IPA) groups the expressed genes into biological mechanisms that aremainly related to drug metabolism. In the top canonical pathways, Oxidative ethanol degradation III together with Fatty Acid α-oxidation may be significant pathways for lambda-cyhalothrin. Our results may provide further understanding of molecular aspects involved in lambda-cyhalothrin-induced liver injury.Item Plasma and Tissue Depletion of Florfenicol and Florfenicol-amine in Chickens(Journal of Agricultural and Food Chemistry, 2008) Anadón Navarro, Arturo Ramón; Martínez Caballero, María Aranzazu; Martínez Caballero, Marta; Ares Lombán, Irma; Martínez Larrañaga, María Rosa; Ríos, Alba; Caballero, VirginiaChickens 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.Item 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(Food and Chemical Toxicology, 2020) Martínez Caballero, María Aranzazu; Ares Lombán, Irma; Martínez Caballero, Marta; López Torres, Bernardo; Rodríguez, José Luis; Maximiliano Guerra, Jorge Enrique; Martínez Larrañaga, María Rosa; Anadón Navarro, Arturo Ramón; Rosa, José Manuel de la; Cueto, MercedesThe 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.Item Fipronil induces CYP isoforms in rats(Food and Chemical Toxicology, 2015) Ares Lombán, Irma; Martínez Caballero, Marta; Martínez Larrañaga, María Rosa; Anadón Navarro, Arturo Ramón; Martínez Caballero, María Aranzazu; Caballero, M.V.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 enzymes