Hypothermia can reverse hepatic oxidative stress damage induced by hypoxia in rats

J Physiol Biochem. 2016 Dec;72(4):615-623. doi: 10.1007/s13105-016-0500-x. Epub 2016 Jul 8.

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, 4-HNE protein adduct amounts were significantly lower in 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.

MeSH terms

  • Aldehydes / metabolism
  • Animals
  • Antioxidants / metabolism*
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / therapy*
  • Glutathione / metabolism
  • Hypothermia, Induced*
  • Hypoxia / metabolism*
  • Hypoxia / pathology
  • Lipid Peroxidation
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Oxygen / adverse effects
  • Protein Carbonylation
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Aldehydes
  • Antioxidants
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Glutathione
  • 4-hydroxy-2-nonenal
  • Oxygen