Maisanaba, Sara

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Universidad Pablo de Olavide
Biología Molecular e Ingeniería Bioquímica
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Ciencias Forenses y Toxicología
Ciencia y Técnicas de la Salud
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Now showing 1 - 10 of 11
  • Publication
    (Amino)cyclophosphazenes as Multisite Ligands for the Synthesis of Antitumoral and Antibacterial Silver(I) Complexes
    (ACS Publications, 2020-01-27) Gascón, Elena; Maisanaba, Sara; Otal, Isabel; Valero Blanco, Eva María; Repetto, Guillermo; Jones, Peter G; Jiménez, Josefina
    The reactivity of the multisite (amino)cyclotriphosphazene ligands, [N3P3(NHCy)6] and [N3P3(NHCy)3(NMe2)3], has been explored in order to obtain silver(I) metallophosphazene complexes. Two series of cationic silver(I) metallophosphazenes were obtained and characterized: [N3P3(NHCy)6{AgL}n](TfO)n [n = 2, L = PPh3 (2), PPh2Me (4); n = 3, L = PPh3 (3), PPh2Me (5), TPA (TPA = 1,3,5-triaza-7-phosphaadamantane, 6)] and nongem-trans-[N3P3(NHCy)3(NMe2)3{AgL}n](TfO)n [n = 2, L = PPh3 (7), PPh2Me (9); n = 3, L = PPh3 (8), PPh2Me (10)]. 5, 7, and 9 have also been characterized by single-crystal X-ray diffraction, thereby allowing key bonding information to be obtained. Compounds 2–6, 9, and 10 were screened for in vitro cytotoxic activity against two tumor human cell lines, MCF7 (breast adenocarcinoma) and HepG2 (hepatocellular carcinoma), and for antimicrobial activity against five bacterial species including Gram-positive, Gram-negative, and Mycobacteria strains. Both the IC50 and MIC values revealed excellent biological activity for these metal complexes, compared with their precursors and cisplatin and also AgNO3 and silver sulfadiazine, respectively. Both IC50 and MIC values are among the lowest values found for any silver derivatives against the cell lines and bacterial strains used in this work. The structure–activity relationships were clear. The most cytotoxic and antimicrobial derivatives were those with the triphenylphosphane and [N3P3(NHCy)6] ligands. A significant improvement in the activity was also observed upon a rise in the number of silver atoms linked to the phosphazene ring.
  • Publication
    Cytotoxic and mutagenic in vitro assessment of two organosulfur compounds derived from onion to be used in the food industry
    (Elsevier, 2014-06-16) Llana Ruíz-Cabello, María; Maisanaba, Sara; Gutiérrez-Praena, Daniel; Prieto, Ana Isabel; Pichardo, Silvia; Jos, Angeles; Moreno, Francisco Javier; Cameán, Ana María
    Edible members of the Allium family are widely used since they exhibit antioxidant and antibacterial related to the organosulphur compounds. One the most promising use of Allium species, hence, onion essential oil, could be in the packaging food industry. The present work aims to assess the safety of two organosulphur compounds present in onion essential oil; dipropyl disulphide, dipropyl sulphide and their mixture. For this purpose, cytotoxicity, reactive oxygen species and glutathione contents, and ultrastructural cellular damages were studied in the human intestinal cells, Caco-2, exposed to these organosulphur compounds. Moreover, their potential mutagenicity was also assessed. The results revealed no significant adverse effects. Additionally, reactive oxygen species scavenger activity was observed for both compounds. Therefore, they could be a good natural alternative to other synthetic antioxidant and antibacterial substances used in the food industry.
  • Publication
    Bioaccessibility and decomposition of cylindrospermopsin in vegetables matrices after the application of an in vitro digestion model
    (Elsevier, 2018-07-06) Maisanaba, Sara; Guzmán-Guillén, Remedios; Valderrama, Rocío; Meca, Giuseppe; Font, Guillermina; Jos, Ángeles; Cameán, Ana M
    Research on the human exposure to Cylindrospermopsin (CYN) via consumption of contaminated food is of great interest for risk assessment purposes. The aim of this work is to evaluate for the first time the CYN bioaccessibility in contaminated vegetables (uncooked lettuce and spinach, and boiled spinach) after an in vitro digestion model, including the salivar, gastric and duodenal phases and, colonic fermentation under lactic acid bacteria. The results obtained showed that the digestion processes are able to diminish CYN levels, mainly in the colonic phase, especially in combination with the boiling treatment, decreasing CYN levels in a significant way. Moreover, the potential decomposition products in a pure CYN solution and in CYN-contaminated vegetables were evaluated using UHPLC-MS/MS Orbitrap. Under the conditions assayed, only two diastereoisomers of the same fragment with m/z 292.09617 have been detected in all the analysed samples, with the exception of digested vegetables. Therefore, in terms of risk assessment, the digestion seems to play an important role in reducing the final bioaccesibility of CYN, and the consumption of cooked vegetables (spinach) would be safer in comparison to raw vegetables.
  • Publication
    Gold(I) metallocyclophosphazenes with antibacterial potency and antitumor efficacy. Synergistic antibacterial action of a heterometallic gold and silver-cyclophosphazene
    (Royal Society of Chemistry, 2022-08-22) Gascón, Elena; Otal, Isabel; Maisanaba, Sara; Llana Ruíz-Cabello, María; Valero Blanco, Eva María; Repetto, Guillermo; Jones, Peter G; Oriol, Luis; Jiménez, Josefina
    One of the most important uses of phosphazenes today involves its biomedical applications. They can also be employed as scaffolds for the design and construction of a variety of ligands in order to coordinate them to metallic drugs. The coordination chemistry of the (amino)cyclotriphosphazene ligand, [N3P3(NHCy)6], towards gold(I) complexes has been studied. Neutral complexes, [N3P3(NHCy)6{AuX}n] (X = Cl or C6F5; n = 1 or 2) (1–4), cationic complexes, [N3P3(NHCy)6{Au(PR3)}n](NO3)n (PR3 = PPh3, PPh2Me, TPA; n = 1, 2 or 3) (6–12) [TPA = 1,3,5-triaza-7-phosphaadamantane] and a heterometallic compound [N3P3(NHCy)6{Au(PPh3)}2{Ag(PPh3)}] (NO3)3 (13) have been obtained and characterized by various methods including single-crystal X-ray diffraction for 7, which confirms the coordination of gold atoms to the nitrogens of the phosphazene ring. Compounds 1, 4, 6–13 were screened for in vitro cytotoxic activity against two tumor human cell lines, MCF7 (breast adenocarcinoma) and HepG2 (hepatocellular carcinoma), and for antimicrobial activity against five bacterial species including Gram-positive, Gram-negative, and Mycobacteria. Both the median inhibitory concentration (IC50) and minimum inhibitory concentration (MIC) values are among the lowest found for any gold or silver derivatives against the cell lines and particularly against the Gram-positive (S. aureus) strain and the mycobacteria used in this work. Structure–activity relationships are discussed in order to determine the influence of ancillary ligands and the number and type of metal atoms (silver or gold). Compounds 4 and 8 showed not only maximal potency on human cells but also some tumour selectivity. Remarkably, compound 13, with both gold and silver atoms, showed outstanding activity against both Gram-positive and Gram-negative strains (nanomolar range), thus having a cooperative effect between gold and silver, with MIC values which are similar or lower than those of gentamicine, ciprofloxacin and rifampicine. The broad spectrum antimicrobial efficacy of all these metallophosphazenes and particularly of heterometallic compound 13 could be very useful to obtain materials for surfaces with antimicrobial properties that are increasingly in demand.
  • Publication
    Plastics in Cyanobacterial Blooms—Genotoxic E ects of Binary Mixtures of Cylindrospermopsin and Bisphenols in HepG2 Cells
    (MDPI, 2020-03-31) Hercog, Klara; Stern, Alja; Maisanaba, Sara; Filipic, Metka; Zegura, Bojana
    Ever-expanding environmental pollution is causing a rise in cyanobacterial blooms and the accumulation of plastics in water bodies. Consequently, exposure to mixtures of cyanotoxins and plastic-related contaminants such as bisphenols (BPs) is of increasing concern. The present study describes genotoxic e ects induced by co-exposure to one of the emerging cyanotoxins—cylindrospermopsin (CYN)—(0.5 g/mL) and BPs (bisphenol A (BPA), S (BPS), and F (BPF); (10 g/mL)) in HepG2 cells after 24 and 72 h of exposure. The cytotoxicity was evaluated with an MTS assay and genotoxicity was assessed through the measurement of the induction of DNA double strand breaks (DSB) with the H2AX assay. The deregulation of selected genes (xenobiotic metabolic enzyme genes, DNA damage, and oxidative response genes) was assessed using qPCR. The results showed a moderate reduction of cell viability and induction of DSBs after 72 h of exposure to the CYN/BPs mixtures and CYN alone. None of the BPs alone reduced cell viability or induced DSBs. No significant di erence was observed between CYN and CYN/BPs exposed cells, except with CYN/BPA, where the antagonistic activity of BPA against CYN was indicated. The deregulation of some of the tested genes (CYP1A1, CDKN1A, GADD45A, and GCLC) was more pronounced after exposure to the CYN/BPs mixtures compared to single compounds, suggesting additive or synergistic action. The present study confirms the importance of co-exposure studies, as our results show pollutant mixtures to induce e ects di erent from those confirmed for single compounds.
  • Publication
    Genotoxic activity of bisphenol A and its analogues bisphenol S, bisphenol F and bisphenol AF and their mixtures in human hepatocellular carcinoma (HepG2) cells
    (Elsevier, 2019-06-06) Hercog, Klara; Maisanaba, Sara; Filipic, Metka; Sollner-Dolenc, Marija; Kac, Lidija; Zegura, Bojana
    The use of bisphenol A (BPA) in manufacturing of plastics is being gradually replaced by presumably safer analogues such as bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF). Despite their widespread occurrence in the environment, there is a knowledge gap in their toxicological profiles. We investigated cytotoxic/ genotoxic effects as well as changes in the expression of selected genes involved in the xenobiotic metabolism, response to oxidative stress and DNA damage upon exposure to BPs and their mixtures in human hepatocellular carcinoma HepG2 cells. BPS and BPF slightly decreased the viability of HepG2 cells,while BPAF was the most cytotoxic compound tested. BPA, BPF and BPAF induced the formation of DNA double strand breaks determinedwith γH2AX assay,while BPS was inactive (5–20 μg/mL). All four BPs up-regulated the expression of CYP1A1 and UGT1A1, while BPS upregulated and BPAF down-regulated also the expression of GST1A. Only BPA up-regulated oxidative stress responsive gene GCLC, while BPAF up-regulated the expression of CDKN1A and GADD45a. At concentrations relevant for human exposure (ng/mL range) BPA and its analogues as individual compounds and in mixtures did not exert genotoxic activity, whereas BPA and BPAF as well as the mixtures up-regulated the expressions of CYP1A1 and UGT1A1.
  • Publication
    Use of micronucleus and comet assay to evaluate evaluate the genotoxicity of oregano essential oil (Origanum vulgare l. Virens) in rats orally exposed for 90 days
    (Taylor and Francis, 2018-03-14) Llana Ruíz-Cabello, María; Puerto, María; Maisanaba, Sara; Pichardo, Silvia; Cameán, Ana María
    Essential oils from Origanum spp. exhibit antioxidant and antimicrobial activities making them suitable for use as food additives. The incorporation of oregano essential oil in active food packaging is under study; however, it has been not authorized for this purpose thus far. In order to fulfill the requirements of the European Food Safety Authority (EFSA), the aim of the present study was to determine the genotoxic potential of oregano essential oil using both the micronucleus (MN) test and comet (standard and enzyme-modified) assays in Wistar rats treated with 50, 100, or 200 mg/kg body weight administered daily for 90 days. MN was performed in cells from the bone marrow and standard and enzyme-modified comet assays were conducted in stomach, liver and blood cells. The major compound detected in the analytical study of oregano essential oil from Origanum vulgare L. virens, was carvacrol (55.82%) followed by thymol (5.14%), as well as their precursors, γ-terpinene (16.39%), and ρ-cimne (4.71%). The results obtained in the genotoxicity assays indicated lack of effect in MN and standard comet assay under the conditions tested. Furthermore, no apparent oxidative damage was observed in the enzyme-modified comet assay in any of the tissues examined of rats exposed to oregano essential oil for 90 days. Therefore, this oregano essential oil appears to be safe in Wistar rats and might be considered as a potential active material in food packaging industry.
  • Publication
    Investigation of mechanisms of toxicity and exclusion by transporters of the preservatives triclosan and propylparaben using batteries of Schizosaccharomyces pombe strains
    (Elsevier, 2019-11-30) Álvarez Herrera, C.; Maisanaba, Sara; Repetto, Guillermo
    Triclosan (TCS) and propylparaben (PPB) are antimicrobials widely used. They present many similarities in their applications and also in their human and environmental health risks. In order to investigate the mechanisms of toxic action and the efflux pumps involved in their detoxication, we used a strategy with batteries of Schizosaccharomyces pombe yeast strains, either defective in cell signalling, in detoxification pumps, or in cell surveillance mechanisms. Yeast were exposed up to 20 h in solid medium or in liquid medium in 96-well plates. The mechanisms of action investigated were spindle defects (mph1), stress (pmk1), DNA interference (rad3) or diverse effects (MDR-sup). The efflux pumps investigated were Bfr1, Pmd1, Mfs1 and Caf5 or the Pap1 transcription factor. Here we show that TCS was 75 times more toxic than PPB in the wild type fission yeast. More oxidative stress and less protection by exclusion pumps were observed for TCS than for PPB. The cytotoxicity produced by TCS decreased from bfr1>mfs1>pmd1 > pap1 and caf5A deficient strains. In contrast, cytotoxic concentrations of PPB caused only a mild stress. The protection provided for PPB by the transporters was more marked than for TCS, decreasing from Pmd1, Caf5, Mfs1 and Bfr1. Furthermore, microtubule and DNA interferences were revealed for PPB, according to the cytotoxicity of mph1 and rad3 defective cells, respectively. As both compounds present complex adverse effects at concentrations close to exposure, and their combination clearly causes a strong potentiation, more exhaustive controls and regulations in their use should be considered.
  • Publication
    In vitro toxicity evaluation of new silane-modified clays and the migration extract from a derived polymer-clay nanocomposite intended to food packaging applications
    (Elsevier, 2017-08-02) Maisanaba, Sara; Guzmán-Guillén, Remedios; Puerto, María; Gutiérrez-Praena, Daniel; Ortuño, Natalia; Jos, Ángeles
    The clay montmorillonite (Mt) is among the nanofillers more frequently used for food packaging applications. The organomodification of clays with different modifiers, such as silanes, is an important step in the preparation of improved polymer/clay materials known as nanocomposites. However, the toxicological data about these nanofillers is still scarce. In the present study, an in vitro toxicological evaluation in Caco-2 cells of two silane-modified clays based on Mt, Clay3 and Clay4 (0–250 g/ml), was performed. The cytotoxicity, cell death, genotoxicity and oxidative stress produced by both organoclays were evaluated after 24 and 48 h of exposure. Moreover, the migration extracts obtained from nanocomposites of polypropylene (PP) + Clay3 and only PP were also investigated. Only Clay4 induced cytotoxicity, showing a reduction of cell viability to 63% of the control, as well as oxidative stress in a concentration-dependent manner. Regarding the PP-Clay3 migration extract, no cytotoxic effects were observed after exposure to the tested concentrations (0–100%). Moreover, significant differences in the presence of Ca, Mg and Si compared to the PP extract were obtained, although migration levels were in accordance with the food contact materials regulation. These findings indicate that a case-by-case toxicological assessment of organoclays should be performed.
  • Publication
    A subchronic 90-day oral toxicity study of Origanum vulgare essential oil in rats
    (Elsevier, 2017-01-03) Llana Ruíz-Cabello, María; Maisanaba, Sara; Puerto, Maria; Pichardo, Silvia; Jos, Angeles; Moyano, Rosario; Cameán, Ana María
    Oregano essential oil (Origanum vulgare L. virens) (OEO) is being used in the food industry due to its useful properties to develop new active packaging systems. In this concern, the safety assessment of this natural extract is of great interest before being commercialized. The European Food Safety Authority requests different in vivo assays to ensure the safety of food contact materials. One of these studies is a 90 days repeated-dose oral assay in rodents. In the present work, 40 male and 40 female Wistar rats were orally exposed to 50, 100 and 200 mg/kg body weight (b.w.) OEO during 90 days following the OECD guideline 408. Data revealed no mortality and no treatment-related adverse effects of the OEO in food/ water consumption, body weight, haematology, biochemistry, necropsy, organ weight and histopathology. These findings suggest that the oral no-observed-adverse-effect level (NOAEL) of this OEO is 200 mg/kg b.w. in Wistar rats, the highest dose tested. In conclusion, the use of this OEO in food packaging appears to be safe based on the lack of toxicity during the subchronic study at doses 330-fold higher than those expected to be in contact consumers in the worst scenario of exposure.