OLIVARES, MARIA BELEN

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OLIVARES, MARIA BELEN
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molivares@udd.cl
ORCID
0000-0001-6950-8433
Scopus Author ID
57194227842
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    Scopus© Citations 1  6
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    Innate gut microbiota predisposes to high alcohol consumption
    (2021)
    EZQUER, EDUARDO FERNANDO  
    ;
    Maria Elena Quintanilla
    ;
    Francisco Moya‐Flores
    ;
    Paola Morales
    ;
    MUNITA SEPULVEDA, JOSE MANUEL  
    Scopus© Citations 34  5
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      6Scopus© Citations 126
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    Analysis of the Behavior of Deep Eutectic Solvents upon Addition of Water: Its Effects over a Catalytic Reaction
    (2024)
    CAMPODONICO GALDAMES, PAOLA ROSSANA  
    ;
    Jazmín Alarcón-Espósito
    ;
    ALCAZAR JIMENEZ, JACKSON JOSE  
    ;
    OLIVARES, MARIA BELEN  
    ;
    SUAREZ ROZAS, CRISTIAN IGNACIO  
    <jats:p>This study presents the potential role of deep eutectic solvents (DESs) in a lipase-catalyzed hydrolysis reaction as a co-solvent in an aqueous solution given by a phosphate buffer. Ammonium salts, such as choline chloride, were paired with hydrogen bond donors, such as urea, 1,2,3-propanetriol, and 1,2 propanediol. The hydrolysis of p-nitrophenyl laureate was carried out with the lipase Candida antarctica Lipase B (CALB) as a reaction model to evaluate the solvent effect and tested in different DES/buffer phosphate mixtures at different % w/w. The results showed that two mixtures of different DES at 25 % w/w were the most promising solvents, as this percentage enhanced the activities of CALB, as evidenced by its higher catalytic efficiency (kcatKM). The solvent analysis shows that the enzymatic reaction requires a reaction media rich in water molecules to enable hydrogen-bond formation from the reaction media toward the enzymatic reaction, suggesting a better interaction between the substrate and the enzyme-active site. This interaction could be attributed to high degrees of freedom influencing the enzyme conformation given by the reaction media, suggesting that CALB acquires a more restrictive structure in the presence of DES or the stabilized network given by the hydrogen bond from water molecules in the mixture improves the enzymatic activity, conferring conformational stability by solvent effects. This study offers a promising approach for applications and further perspectives on genuinely green industrial solvents.</jats:p>
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    A Novel Morphine Drinking Model of Opioid Dependence in Rats
    (2022)
    BERRIOS CARCAMO, PABLO ANDRES  
    ;
    Mauricio Quezada
    ;
    Daniela Santapau
    ;
    Paola Morales
    ;
    OLIVARES, MARIA BELEN  
    <jats:p>An animal model of voluntary oral morphine consumption would allow for a pre-clinical evaluation of new treatments aimed at reducing opioid intake in humans. However, the main limitation of oral morphine consumption in rodents is its bitter taste, which is strongly aversive. Taste aversion is often overcome by the use of adulterants, such as sweeteners, to conceal morphine taste or bitterants in the alternative bottle to equalize aversion. However, the adulterants’ presence is the cause for consumption choice and, upon removal, the preference for morphine is not preserved. Thus, current animal models are not suitable to study treatments aimed at reducing consumption elicited by morphine itself. Since taste preference is a learned behavior, just-weaned rats were trained to accept a bitter taste, adding the bitterant quinine to their drinking water for one week. The latter was followed by allowing the choice of quinine or morphine (0.15 mg/mL) solutions for two weeks. Then, quinine was removed, and the preference for morphine against water was evaluated. Using this paradigm, we show that rats highly preferred the consumption of morphine over water, reaching a voluntary morphine intake of 15 mg/kg/day. Morphine consumption led to significant analgesia and hyperlocomotion, and to a marked deprivation syndrome following the administration of the opioid antagonist naloxone. Voluntary morphine consumption was also shown to generate brain oxidative stress and neuroinflammation, signs associated with opioid dependence development. We present a robust two-bottle choice animal model of oral morphine self-administration for the evaluation of therapeutic interventions for the treatment of morphine dependence.</jats:p>
    Scopus© Citations 13  1
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    Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use
    (2023)
    María Elena Quintanilla
    ;
    Paola Morales
    ;
    Daniela Santapau
    ;
    Alba Ávila
    ;
    Carolina Ponce
    <jats:p>Chronic opioid intake leads to several brain changes involved in the development of dependence, whereby an early hedonistic effect (liking) extends to the need to self-administer the drug (wanting), the latter being mostly a prefrontal–striatal function. The development of animal models for voluntary oral opioid intake represents an important tool for identifying the cellular and molecular alterations induced by chronic opioid use. Studies mainly in humans have shown that polydrug use and drug dependence are shared across various substances. We hypothesize that an animal bred for its alcohol preference would develop opioid dependence and further that this would be associated with the overt cortical abnormalities clinically described for opioid addicts. We show that Wistar-derived outbred UChB rats selected for their high alcohol preference additionally develop: (i) a preference for oral ingestion of morphine over water, resulting in morphine intake of 15 mg/kg/day; (ii) marked opioid dependence, as evidenced by the generation of strong withdrawal signs upon naloxone administration; (iii) prefrontal cortex alterations known to be associated with the loss of control over drug intake, namely, demyelination, axonal degeneration, and a reduction in glutamate transporter GLT-1 levels; and (iv) glial striatal neuroinflammation and brain oxidative stress, as previously reported for chronic alcohol and chronic nicotine use. These findings underline the relevance of polydrug animal models and their potential in the study of the wide spectrum of brain alterations induced by chronic morphine intake. This study should be valuable for future evaluations of therapeutic approaches for this devastating condition.</jats:p>
      7Scopus© Citations 6
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    Exploring the behavior of Candida antarctica lipase B in aqueous mixtures of an imidazolium ionic liquid and its surfactant analogue
    (2023)
    CAMPODONICO GALDAMES, PAOLA ROSSANA  
    ;
    Cristian Calderón
    ;
    Jackson J. Alcázar  
    ;
    OLIVARES, MARIA BELEN  
    ;
    Limberg Jaldin
    <jats:p>The performance of <jats:italic>Candida antarctica</jats:italic> lipase B (CALB) has been evaluated in 1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF<jats:sub>4</jats:sub>)/water mixtures in a wide range of molar fractions (<jats:inline-formula><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="m1"><mml:mrow><mml:msub><mml:mi mathvariant="normal">χ</mml:mi><mml:mrow><mml:mi>B</mml:mi><mml:mi>M</mml:mi><mml:mi>I</mml:mi><mml:mi>M</mml:mi><mml:mi>B</mml:mi><mml:mi>F</mml:mi><mml:mn>4</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math></jats:inline-formula>) with and without 1-dodecyl-3-methylimidazolium tetrafluoroborate (C<jats:sub>12</jats:sub>-MIMBF<jats:sub>4</jats:sub>), a surfactant derived from BMIMBF<jats:sub>4</jats:sub>. The main aim of this work is to evaluate the influence of <jats:inline-formula><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="m2"><mml:mrow><mml:msub><mml:mi mathvariant="normal">χ</mml:mi><mml:mrow><mml:mi>B</mml:mi><mml:mi>M</mml:mi><mml:mi>I</mml:mi><mml:mi>M</mml:mi><mml:mi>B</mml:mi><mml:mi>F</mml:mi><mml:mn>4</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math></jats:inline-formula> over micellar aggregates to assess the activity of enzymatic reactions. The investigated reaction corresponds to the hydrolysis of the substrate <jats:italic>p</jats:italic>-nitrophenyl laureate in each <jats:inline-formula><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="m3"><mml:mrow><mml:msub><mml:mi mathvariant="normal">χ</mml:mi><mml:mrow><mml:mi>B</mml:mi><mml:mi>M</mml:mi><mml:mi>I</mml:mi><mml:mi>M</mml:mi><mml:mi>B</mml:mi><mml:mi>F</mml:mi><mml:mn>4</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math></jats:inline-formula>. The kinetic study for <jats:inline-formula><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="m4"><mml:mrow><mml:msub><mml:mi mathvariant="normal">χ</mml:mi><mml:mrow><mml:mi>B</mml:mi><mml:mi>M</mml:mi><mml:mi>I</mml:mi><mml:mi>M</mml:mi><mml:mi>B</mml:mi><mml:mi>F</mml:mi><mml:mn>4</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math></jats:inline-formula> at around 0.2 proved to be a border point in enzymatic activity. At <jats:inline-formula><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="m5"><mml:mrow><mml:msub><mml:mi mathvariant="normal">χ</mml:mi><mml:mrow><mml:mi>B</mml:mi><mml:mi>M</mml:mi><mml:mi>I</mml:mi><mml:mi>M</mml:mi><mml:mi>B</mml:mi><mml:mi>F</mml:mi><mml:mn>4</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math></jats:inline-formula> = 0.1, the lipase activity increases in the presence of C<jats:sub>12</jats:sub>-MIMBF<jats:sub>4</jats:sub>. However, at higher concentrations, BMIMBF<jats:sub>4</jats:sub> has a negligible effect over the lipase activity. These results suggest specific interactions between water and BMIMBF<jats:sub>4</jats:sub> molecules in relation to CALB. This research highlights the superactivity phenomenon driven by the reaction media and the micelle interface. In this interfacial interaction, BMIMBF<jats:sub>4</jats:sub> acts directly on the changes induced on the enzyme upon its interaction with the micellar interface. This study opens a green perspective toward the biocatalysis field.</jats:p>
      12Scopus© Citations 4