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


OBJECTIVE
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 (O211%) 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.


CONCLUSIONS
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.
1 Drug Applied Research Center of Tabriz University of Medical Sciences , Tabriz, Iran .
Hasan
H
Omrani
2 Neurosciences Research Center of Tabriz University of Medical Sciences , Tabriz, Iran .
Mohammad Reza
MR
Alipour
2 Neurosciences Research Center of Tabriz University of Medical Sciences , Tabriz, Iran .
Fereshteh
F
Farajdokht
1 Drug Applied Research Center of Tabriz University of Medical Sciences , Tabriz, Iran .
Hadi
H
Ebrahimi
1 Drug Applied Research Center of Tabriz University of Medical Sciences , Tabriz, Iran .
Mehran
M
Mesgari Abbasi
1 Drug Applied Research Center of Tabriz University of Medical Sciences , Tabriz, Iran .
Gisou
G
Mohaddes
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000187:drug effects*; D002908:Chronic Disease; D004195:Disease Models, Animal; D054439:Ghrelin / Q000008:administration & dosage*; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007249:Inflammation; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D054439:Ghrelin; D014409:Tumor Necrosis Factor-alpha
TNF-α; brain; ghrelin; oxidative stress; rat; systemic hypoxia