Antioxidative effects of uridine in a neonatal rat model of hyperoxic brain injury

Abstract

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.

One-to-one Benefit provided by Antioxidants to cultured skin Fibroblasts from Friedreich Ataxia patients

“…In the presence of Pyruvate, the deleterious effect of stressing conditions was much less pronounced, being roughly annihilated and strongly reduced by Uridine for 4 of the 5 patients. Uridine and pyruvate have been described previously as neuroprotective compounds [33], our results confirmed their protective effects against oxidative stress in FRDA fibroblasts. Throughout this study, we were unable to evidence any positive effect of the glitazone (Pioglitazone) on the small number of FRDA fibroblasts tested.…”

“…Using precisely the five cell lines derived from FRDA patients for which we previously gather a set of molecular and biochemical data, we here underlines the one-to-one response to three substances known to exert antioxidant effects by distinct mechanisms (Fig. 1) : Uridine, acting particularly on the antioxidant signaling pathway of SOD1 (cytosolic and mitochondrial intermembrane location) [33] through the glyoxalase DJ-1 [34,35]; Pyruvate, a potent hydrogen peroxide detoxifying agent through a nonenzymatic reaction specific to dicarboxylic acids [36]; Pioglitazone acting on antioxidant defenses signaling, in particular of mitochondrial SOD2, via the Nrf2 transcription factor to rescue cells mortality in FRDA [37]. PIP5K1β, phosphatidylinositol-4-phosphate 5-kinase type 1 β; ERK1/2, extracellular signalregulated kinase 1/2 cascade; DJ-1, a glyoxalase [34] [35]) also known as Parkinson protein 7 (Park7); Nrf2, nuclear factor (erythroid-derived 2)-like 2; SOD, superoxide dismutase.…”

Evaluating Neuroprotective Effects of Uridine, Erythropoietin, and Therapeutic Hypothermia in a Ferret Model of Inflammation-Sensitized Hypoxic-Ischemic Encephalopathy

“…When administered at a dose of 500 mg/kg for three consecutive days, Ur provided modest neuroprotection in a rat model of HIE [ 14 , 23 ]. The neuroprotective effects of Ur administration in rodents seems to be mediated through its antiapoptotic [ 14 ] and antioxidant actions [ 24 ]. However, despite being administered at a similar dose, Ur was not neuroprotective in this model and may have contributed to the increase in mortality.…”

The effect of extended continuous nursing strategy applied to patients with mild brain injury on their quality of life and self-efficacy

“…The scale contains a total of 7 dimensions, and the score of each dimension is 0–100 score. It indicates that the quality of life level of the corresponding dimension is better ( 7 ).…”