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Ezquer, Fernando

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Author: Ezquer, Marcelo × End date: 2024 ×

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Now showing 1 - 3 of 3
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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) Ezquer, Fernando; Ezquer, Marcelo; Gallardo, Javiera; Quintanilla, María; Morales, Paola; Santapau, Daniela; Ávila, Alba; Ponce, Carolina; Berrios, Pablo; Olivares, Belén; Herrera, Mario; Israel, Yedy
    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.
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    Administration of Secretome Derived from Human Mesenchymal Stem Cells Induces Hepatoprotective Effects in Models of Idiosyncratic Drug-Induced Liver Injury Caused by Amiodarone or Tamoxifen
    (2023) Huang, Ya-Lin; De Gregorio, Cristian; Silva, Verónica; Elorza, Álvaro; Léniz, Patricio; Aliaga, Víctor; Maracaja, Vinicius; Budini, Mauricio; Ezquer, Fernando; Ezquer, Marcelo
    Drug-induced liver injury (DILI) is one of the leading causes of acute liver injury. While many factors may contribute to the susceptibility to DILI, obese patients with hepatic steatosis are particularly prone to suffer DILI. The secretome derived from mesenchymal stem cell has been shown to have hepatoprotective effects in diverse in vitro and in vivo models. In this study, we evaluate whether MSC secretome could improve DILI mediated by amiodarone (AMI) or tamoxifen (TMX). Hepatic HepG2 and HepaRG cells were incubated with AMI or TMX, alone or with the secretome of MSCs obtained from human adipose tissue. These studies demonstrate that coincubation of AMI or TMX with MSC secretome increases cell viability, prevents the activation of apoptosis pathways, and stimulates the expression of priming phase genes, leading to higher proliferation rates. As proof of concept, in a C57BL/6 mouse model of hepatic steatosis and chronic exposure to AMI, the MSC secretome was administered endovenously. In this study, liver injury was significantly attenuated, with a decrease in cell infiltration and stimulation of the regenerative response. The present results indicate that MSC secretome administration has the potential to be an adjunctive cell-free therapy to prevent liver failure derived from DILI caused by TMX or AMI.
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    A Natural deep eutectic solvent as an effective material for dual debridement and antibiofilm effects in chronic wound treatment
    (2024) Map, Christina; Ezquer, Fernando; Mamani, Sigde; Campodónico, Paola; Cárcamo, Constanza; Martinez, Fabián; Aburto, Isabel; Ezquer, Marcelo; Morales, Bernardo; Olivares, Belén
    In chronic wound treatment, the debridement of devitalized tissue and the eradication of the biofilm must balance aggressiveness with care to protect regenerating tissues. In this study, urea, a potent chaotropic molecule, was modulated through the formation of a Natural Deep Eutectic Solvent (NADES) with betaine to develop a new debriding material (BU) suitable for application into injured dermal tissues. To evaluate BU's debriding capacity, along with its antibiofilm effect and biocompatibility, pre-clinical to clinical methods were employed. In vitro determinations using artificial and clinical slough samples indicate that BU has a high debriding capacity. Additionally, BU's de-structuring effects lead to a strong antibiofilm capability, demonstrated by a reduced bacterial load compared to the antiseptic PHMB-Betaine or medical honey, evaluated in artificial slough and ex vivo human skin. Furthermore, BU's efficacy was evaluated in a murine model of diabetic wound, demonstrating significant effects on debriding and antibiofilm capacity, similar to those observed in PHMB-Betaine and medical honey-treated animals. Finally, BU was clinically evaluated in leg ulcers, showing superiority in reduction of bacterial load and wound area compared to honey, with no adverse effects. Thus, BU represents a simple and non-biocidal option that could contributes to chronic wound care.

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