Antioxidative effects of uridine in a neonatal rat model of hyperoxic brain injury
Animals
Animals, Newborn
Antioxidants
/ pharmacology
Brain Injuries
/ drug therapy
Disease Models, Animal
Glutathione Peroxidase
/ drug effects
Hyperoxia
/ complications
Malondialdehyde
/ metabolism
Neuroprotective Agents
/ pharmacology
Peroxidase
/ drug effects
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species
/ metabolism
Superoxide Dismutase
Uridine
DJ-1
Uridine
hyperoxia
antioxidative
neonatal rat
Journal
Turkish journal of medical sciences
ISSN: 1303-6165
Titre abrégé: Turk J Med Sci
Pays: Turkey
ID NLM: 9441758
Informations de publication
Date de publication:
17 12 2020
17 12 2020
Historique:
received:
03
02
2020
accepted:
31
05
2020
entrez:
4
6
2020
pubmed:
4
6
2020
medline:
12
10
2021
Statut:
epublish
Résumé
Premature birth is a major problem that results in an increased risk of mortality and morbidity. The management of such infants consists of supraphysiological oxygen therapy, which affects brain development due, in part, to the deterioration caused by reactive oxygen species (ROS). We showed previously that exogenously administered uridine provides neuroprotection in a neonatal rat model of hyperoxic brain injury. Hence, the aim of the present study was to investigate the effects of uridine on ROS in the same setting. Hyperoxic brain injury was induced by subjecting a total of 53 six-day-old rat pups to 80% oxygen (the hyperoxia group) for a period of 48 h. The pups in the normoxia group continued breathing room air (21% oxygen). Normoxia + saline or hyperoxia + saline or hyperoxia + uridine 100 mg/kg or hyperoxia + uridine 300 mg/kg or hyperoxia + uridine 500 mg/kg was injected intraperitoneally (i. p.) 15 min prior to the hyperoxia procedure. The pups were decapitated and the brains were homogenized to analyze superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), and malondialdehyde (MDA) enzymes as well as DJ-1 (protein deglycase DJ-1) — an oxidative stress-sensitive protein. Hyperoxia-induced may cause overproduction of oxygen radicals and the oxidant/antioxidant balance may be disturbed in the brain. Brain MPO and MDA levels were significantly increased in saline-receiving pups exposed to hyperoxia. Brain SOD and GSH-Px levels were significantly decreased in saline-receiving pups exposed to hyperoxia. Our results showed that uridine administration prevented the hyperoxia-induced decrease in SOD and GSH-Px while counteracting the hyperoxia-induced increase in MPO and MDA in a dose-dependent manner. Uridine also increased the DJ-1 levels in brains of rat pups subjected to hyperoxia. These data suggest that uridine exhibits antioxidative properties which may mediate the protective effects of uridine in a neonatal rat model of hyperoxic brain injury.
Sections du résumé
Background/aim
Premature birth is a major problem that results in an increased risk of mortality and morbidity. The management of such infants consists of supraphysiological oxygen therapy, which affects brain development due, in part, to the deterioration caused by reactive oxygen species (ROS). We showed previously that exogenously administered uridine provides neuroprotection in a neonatal rat model of hyperoxic brain injury. Hence, the aim of the present study was to investigate the effects of uridine on ROS in the same setting.
Materials and methods
Hyperoxic brain injury was induced by subjecting a total of 53 six-day-old rat pups to 80% oxygen (the hyperoxia group) for a period of 48 h. The pups in the normoxia group continued breathing room air (21% oxygen). Normoxia + saline or hyperoxia + saline or hyperoxia + uridine 100 mg/kg or hyperoxia + uridine 300 mg/kg or hyperoxia + uridine 500 mg/kg was injected intraperitoneally (i. p.) 15 min prior to the hyperoxia procedure. The pups were decapitated and the brains were homogenized to analyze superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), and malondialdehyde (MDA) enzymes as well as DJ-1 (protein deglycase DJ-1) — an oxidative stress-sensitive protein.
Results
Hyperoxia-induced may cause overproduction of oxygen radicals and the oxidant/antioxidant balance may be disturbed in the brain. Brain MPO and MDA levels were significantly increased in saline-receiving pups exposed to hyperoxia. Brain SOD and GSH-Px levels were significantly decreased in saline-receiving pups exposed to hyperoxia. Our results showed that uridine administration prevented the hyperoxia-induced decrease in SOD and GSH-Px while counteracting the hyperoxia-induced increase in MPO and MDA in a dose-dependent manner. Uridine also increased the DJ-1 levels in brains of rat pups subjected to hyperoxia.
Conclusion
These data suggest that uridine exhibits antioxidative properties which may mediate the protective effects of uridine in a neonatal rat model of hyperoxic brain injury.
Substances chimiques
Antioxidants
0
Neuroprotective Agents
0
Reactive Oxygen Species
0
Malondialdehyde
4Y8F71G49Q
Peroxidase
EC 1.11.1.7
Glutathione Peroxidase
EC 1.11.1.9
Superoxide Dismutase
EC 1.15.1.1
Uridine
WHI7HQ7H85
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2059-2066Informations de copyright
This work is licensed under a Creative Commons Attribution 4.0 International License.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest with regard to the present study.