Hypothermia can reverse hepatic oxidative stress damage induced by hypoxia in rats
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ORIGINAL PAPER
Hypothermia can reverse hepatic oxidative stress damage induced by hypoxia in rats Manuel Vicente Garnacho-Castaño & Norma Alva & Sergio Sánchez-Nuño & Raquel G. Bardallo & Jesús Palomeque & Teresa Carbonell
Received: 14 November 2015 / Accepted: 21 June 2016 # University of Navarra 2016
Abstract Our previous findings demonstrated that hypothermia enhances the reduction potential in the liver and helps to maintain the plasmatic antioxidant pool. Here, we aimed to elucidate if hypothermia protects against hypoxia-induced oxidative stress damage in rat liver. Several hepatic markers of oxidative stress were compared in three groups of animals (n = 8 in each group): control normothermic group ventilated with room air and two groups under extreme hypoxia (breathing 10 % O2), one kept at normothermia (HN) (37 °C) and the other under deep hypothermia (HH) (central body temperature of 21–22 °C). Hypoxia in normothermia significantly increased the levels of hepatic nitric oxide, inducible nitric oxide synthase expression, protein oxidation, Carbonilated proteins, advanced oxidation protein products, 4-hydroxynonenal (HNE) protein adducts, and lipid peroxidation when compared to the control group (p < 0.05). However, when hypoxia was induced under hypothermia, results from the oxidative stress biomarker analyses did not differ significantly from those found in the control group. Indeed, 4HNE protein adduct amounts were significantly lower in M. V. Garnacho-Castaño (*) TecnoCampus Mataró-Maresme, College of Health Sciences, University of Pompeu Fabra, Ernest Lluch, 32 (Porta Laietana), 08302 Mataró-Barcelona, Spain e-mail: [email protected] M. V. Garnacho-Castaño : N. Alva : S. Sánchez-Nuño : R. G. Bardallo : J. Palomeque : T. Carbonell Department of Cell Biology, Physiology and Inmunology, Faculty of Biology, University of Barcelona, 643 Diagonal Ave. (3rd floor), 08028 Barcelona, Spain
the HH versus HN group (p < 0.05). Therefore, hypothermia can mitigate hypoxia-induced oxidative stress damage in rat liver. These effects could help clarify the mechanisms of action of therapeutic hypothermia. Keywords 4-HNE adducts . Hypoxia . Lipid peroxidation . Nitric oxide . Protein oxidation . Therapeutic hypothermia
Introduction Hypoxia and hypothermia limit the availability of oxygen in tissues. Oxygen tension in mammals range from 40 mmHg in mixed venous blood and most organs and tissues to up to 150 mmHg in lung apices, with anything lower than 10 mmHg in various pathologies linked to ischemic conditions [33]. Despite this tissue capacity, acute or chronic exposure to hypoxia disrupts the normal functioning of the human body, affecting cardiorespiratory, endocrine, metabolic, nutritional, thermal, and cellular homeostasis [17]. Hypoxia affects the socalled O2 cascade, reducing the diffusion of O2 from atmospheric air to the tissues [27] and inducing oxidative stress in animals and humans [23]. Hypothermia induces redistribution of blood flow and microcirculation perturbations, which also limit tissue ox
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