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Front. Physiol. | doi: 10.3389/fphys.2018.01800

Leptin treatment mediates survival against sepsis through improving hypotension, tachycardia, oxidative stress burst and multiple organ dysfunction

 Alejandro Vallejos1, Pedro Olivares1,  Claudio Cabello-Verrugio1, Claudio Pérez-Leighton2 and  Felipe Simon1*
  • 1Universidad Andrés Bello, Chile
  • 2Pontificia Universidad Católica de Chile, Chile

Sepsis syndrome is the most important cause of mortality in critically ill patients admitted to intensive care units (ICU). However, current therapies for its prevention and treatment are still unsatisfactory, and the mortality rate is still high. Non-septic ICU patients are vulnerable to acquire sepsis syndrome. Thus, a preventive treatment for this population is needed.
During sepsis syndrome and endotoxemia, severe hypotension, tachycardia, oxidative and immune response increase, multiple organ dysfunction syndrome (MODS) and decreased survival are observed.
Leptin administration protects against negative effects of sepsis syndrome and endotoxemia. Furthermore, it is has been reported that leptin elevates blood pressure mediated by sympathetic nervous system activation. However, whether leptin mediates its protective effects during sepsis through blood pressure regulation is not known. Therefore, we investigate whether leptin improves blood pressure and MODS, resulting in survival increase during endotoxemia.
The results showed that leptin treatment reduced both the hypotension and tachycardia characteristically observed during endotoxemia. Notably, this protective effect was observed early and late in the course of endotoxemia. Endotoxemia-induced MODS decreased in leptin-treated rats, which was reflected in normal values for liver and kidney function, inhibition of muscle mass wasting and maintenance of glycemia. Furthermore, leptin treatment decreased the oxidative stress burst in blood and blunted the increased pro-inflammatory cytokines TNF-α, IL-1β and IL-6 observed during endotoxemia. Remarkably, according to the leptin-induced increase in survival, leptin administration decreased the risk for death associated with sepsis syndrome at early and late times after endotoxemia induction.
These results show a potential preventive therapy against sepsis syndrome and endotoxemia in vulnerable patients, based in the beneficial actions of leptin.

Keywords: Endotoxemia, Hypotension, MODS, Oxidative Stress, survial

Received: 02 Aug 2018; Accepted: 29 Nov 2018.

Edited by:

Mauricio A. Retamal, Universidad del Desarrollo, Chile

Reviewed by:

Marilena Kampa, University of Crete, Greece
Elias Castanas, School of Medicine, University of Crete, Greece
Maria Fernandez-Velasco, Hospital Universitario La Paz, Spain
Juan F. Santibanez, University of Belgrade, Serbia  

Copyright: © 2018 Vallejos, Olivares, Cabello-Verrugio, Pérez-Leighton and Simon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Felipe Simon, Universidad Andrés Bello, Santiago, 8320000, Santiago Metropolitan Region (RM), Chile, fsimon@unab.cl