Effects of Chronic Ghrelin Treatment on Hypoxia-Induced Brain Oxidative Stress and Inflammation in a Rat Normobaric Chronic Hypoxia Model

High Alt Med Biol. 2017 Jun;18(2):145-151. doi: 10.1089/ham.2016.0132. Epub 2017 Mar 21.


Omrani, Hasan, Mohammad Reza Alipour, Fereshteh Farajdokht, Hadi Ebrahimi, Mehran Mesgari Abbasi, and Gisou Mohaddes. Effects of chronic ghrelin treatment on hypoxia-induced brain oxidative stress and inflammation in a rat normobaric chronic hypoxia model. High Alt Med Biol. 18:145-151, 2017.

Aim: This study aimed to evaluate the probable antioxidant effects of ghrelin in the brain and serum and its effect on tumor necrosis factor-alpha (TNF-α) levels in the brain in a model of chronic systemic hypoxia in rats.

Methods: Systemic hypoxia was induced by a normobaric hypoxic chamber (O2 11%) for ten days. Adult male Wistar rats were divided into control (C), chronic ghrelin (80 μg/kg/10 days) (Ghr), chronic hypoxia (CH), and CH and ghrelin (80 μg/kg/ip/10 days) (CH + Gh) groups. The activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and malondialdehyde (MDA), total antioxidant capacity, and TNF-α levels were assessed in the serum and brain tissue.

Results: Our results showed that chronic ghrelin administration attenuated the CH-increased oxidative stress by decreasing MDA levels in the serum and brain tissue. Moreover, ghrelin enhanced the antioxidant defense against hypoxia-induced oxidative stress in the serum and brain tissue. Brain TNF-α levels in CH did not change significantly; however, ghrelin significantly (p < 0.001) decreased it.

Conclusion: These results indicated that ghrelin promoted antioxidative and anti-inflammatory defense under chronic exposure to hypoxia. Therefore, ghrelin might be used as a potential therapy in normobaric hypoxia and oxidative stress induced by CH.

Keywords: TNF-α; brain; ghrelin; oxidative stress; rat; systemic hypoxia.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Brain / drug effects*
  • Chronic Disease
  • Disease Models, Animal
  • Ghrelin / administration & dosage*
  • Hypoxia / complications
  • Hypoxia / drug therapy*
  • Hypoxia / physiopathology
  • Inflammation
  • Male
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / metabolism


  • Antioxidants
  • Ghrelin
  • Tumor Necrosis Factor-alpha