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Open AccessArticle

Maresin 1, a Proresolving Lipid Mediator, Ameliorates Liver Ischemia-Reperfusion Injury and Stimulates Hepatocyte Proliferation in Sprague-Dawley Rats

1
Escuela de Tecnología Medica, Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile
2
Programa de Doctorado en Ciencias mención Investigación y Desarrollo de Productos Bioactivos, Instituto de Química de los Recursos Naturales, Universidad de Talca, Talca 3460000, Chile
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Escuela de Medicina, Universidad de Talca, Talca 3460000, Chile
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Departamento de Ciencias Básicas Biomédicas, Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile
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Centro de Bioinformática, Simulación y Modelado, Facultad de Ingeniería, Universidad de Talca, Talca 3460000, Chile
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Unidad de Anatomía Patológica, Hospital Regional de Talca, Talca 3460001, Chile
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Centro Oncológico, Facultad de Medicina, Universidad Católica del Maule, Talca 3466706, Chile
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(2), 540; https://doi.org/10.3390/ijms21020540
Received: 26 November 2019 / Revised: 12 December 2019 / Accepted: 12 December 2019 / Published: 15 January 2020
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics 2020)
Maresin-1 (MaR1) is a specialized pro-resolving mediator, derived from omega-3 fatty acids, whose functions are to decrease the pro-inflammatory and oxidative mediators, and also to stimulate cell division. We investigated the hepatoprotective actions of MaR1 in a rat model of liver ischemia-reperfusion (IR) injury. MaR1 (4 ng/gr body weight) was administered prior to ischemia (1 h) and reperfusion (3 h), and controls received isovolumetric vehicle solution. To analyze liver function, transaminases levels and tissue architecture were assayed, and serum cytokines TNF-α, IL-6, and IL-10, mitotic activity index, and differential levels of NF-κB and Nrf-2 transcription factors, were analyzed. Transaminase, TNF-α levels, and cytoarchitecture were normalized with the administration of MaR1 and associated with changes in NF-κB. IL-6, mitotic activity index, and nuclear translocation of Nrf-2 increased in the MaR1-IR group, which would be associated with hepatoprotection and cell proliferation. Taken together, these results suggest that MaR1 alleviated IR liver injury, facilitated by the activation of hepatocyte cell division, increased IL-6 cytokine levels, and the nuclear localization of Nrf-2, with a decrease of NF-κB activity. All of them were related to an improvement of liver injury parameters. These results open the possibility of MaR1 as a potential therapeutic tool in IR and other hepatic pathologies. View Full-Text
Keywords: liver preconditioning; bioactive lipids; mitotic activity index; cytokines; transcription factors liver preconditioning; bioactive lipids; mitotic activity index; cytokines; transcription factors
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Soto, G.; Rodríguez, M.J.; Fuentealba, R.; Treuer, A.V.; Castillo, I.; González, D.R.; Zúñiga-Hernández, J. Maresin 1, a Proresolving Lipid Mediator, Ameliorates Liver Ischemia-Reperfusion Injury and Stimulates Hepatocyte Proliferation in Sprague-Dawley Rats. Int. J. Mol. Sci. 2020, 21, 540.

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