Person:
Navarro González De Mesa, Elisa

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First Name
Elisa
Last Name
Navarro González De Mesa
URI
https://hdl.handle.net/20.500.14352/79321
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
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Author: Egea, Javier × Subject: 577.2 ×

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Now showing 1 - 2 of 2
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    Microglial HO‐1 induction by curcumin provides antioxidant, antineuroinflammatory, and glioprotective effects
    (Molecular Nutrition & Food Research, 2015) Parada, Esther; Buendia, Izaskun; Navarro González De Mesa, Elisa; Avendaño, Carlos; Egea, Javier; García López, Manuela
    Scope: We have studied if curcumin can protect glial cells under an oxidative stress and inflammatory environment, which is known to be deleterious in neurodegeneration. Methods and results: Primary rat glial cultures exposed to the combination of an oxidative (rotenone/oligomycin A) and a proinflammatory LPS stimuli reduced by 50% glial viability. Under these experimental conditions, curcumin afforded significant glial protection and reduction of reactive oxygen species; these effects were blocked by the HO-1 inhibitor tin protoporphyrin-IX (SnPP). These findings correlate with the observation that curcumin induced the antioxidative protein HO-1. Most interesting was the observation that the glial protective effects related to HO-1 induction were microglial specific as shown in glial cultures from LysM(Cre) Hmox(∆/∆) mice where curcumin lost its protective effect. Under LPS conditions, curcumin reduced the microglial proinflammatory markers iNOS and tumor necrosis factor, but increased the anti-inflammatory cytokine IL4. Analysis of the microglial phenotype showed that curcumin favored a ramified morphology toward a microglial alternative activated state against LPS insult also by a HO-1-dependent mechanism. Conclusion: The curry constituent curcumin protects glial cells and promotes a microglial anti-inflammatory phenotype by a mechanism that implicates HO-1 induction; these effects may have impact on brain protection under oxidative and inflammatory conditions.
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    Melatonin–sulforaphane hybrid ITH12674 induces neuroprotection in oxidative stress conditions by a ‘drug–prodrug’ mechanism of action
    (British Journal of Pharmacology, 2015) Egea, Javier; Buendia, Izaskun; Parada, Esther; Navarro González De Mesa, Elisa; Rada, Patricia; Cuadrado, Antonio; López, Manuela G.; García García, Antonio; León Martínez, Rafael
    Background and purpose: Neurodegenerative diseases are a major problem afflicting ageing populations; however, there are no effective treatments to stop their progression. Oxidative stress and neuroinflammation are common factors in their pathogenesis. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of oxidative stress, and melatonin is an endogenous hormone with antioxidative properties that reduces its levels with ageing. We have designed a new compound that combines the effects of melatonin with Nrf2 induction properties, with the idea of achieving improved neuroprotective properties. Experimental approach: Compound ITH12674 is a hybrid of melatonin and sulforaphane designed to exert a dual drug-prodrug mechanism of action. We obtained the proposed hybrid in a single step. To test its neuroprotective properties, we used different in vitro models of oxidative stress related to neurodegenerative diseases and brain ischaemia. Key results: ITH12674 showed an improved neuroprotective profile compared to that of melatonin and sulforaphane. ITH12674 (i) mediated a concentration-dependent protective effect in cortical neurons subjected to oxidative stress; (ii) decreased reactive oxygen species production; (iii) augmented GSH concentrations in cortical neurons; (iv) enhanced the Nrf2-antioxidant response element transcriptional response in transfected HEK293T cells; and (v) protected organotypic cultures of hippocampal slices subjected to oxygen and glucose deprivation and re-oxygenation from stress by increasing the expression of haem oxygenase-1 and reducing free radical production. Conclusion and implications: ITH12674 combines the signalling pathways of the parent compounds to improve its neuroprotective properties. This opens a new line of research for such hybrid compounds to treat neurodegenerative diseases.