Xanthine Oxidase during Human Fetal Development

Vettenranta, Kim; Raivio, Kari O.

doi:10.1203/00006450-199003000-00017

Cited by 27 publications

(13 citation statements)

References 22 publications

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“…The most likely mechanism affected is that of oxidative stress from NO and NO-derived radicals. The developing fetal brain is most vulnerable to oxidative stress because of immature antioxidant enzyme systems [Mishra and Delivoria-Papadopoulos, 1988;Khan and Black, 2003], early development of prooxidant systems such as xanthine oxidase [Vettenranta and Raivio, 1990] and NOS [Keilhoff et al, 1996], and having a relative deficiency in tetrahydrobiopterin that predisposes to uncoupling of nNOS and the production of superoxide from nNOS [Vásquez-Vivar et al, 1999. NO reacts with available superoxide to form peroxynitrite [Beckman, 1991] and reactive nitrogen species [Bolaños et al, 2009], which are powerful biological oxidants [Knapp et al, 2001].…”

Section: Discussionmentioning

confidence: 99%

Neuronal Nitric Oxide Synthase Inhibition Prevents Cerebral Palsy following Hypoxia-Ischemia in Fetal Rabbits: Comparison between JI-8 and 7-Nitroindazole

Derrick

Ji³

et al. 2011

Dev Neurosci

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moderately and 13 severely affected kits and 5 stillbirths, compared with 8 normal, 3 moderately affected and 5 severely affected kits and 10 stillbirths in the 7-NI group. In terms of neurobehavioral outcome, 7-NI was not different from saline treatment, while JI-8 was superior to saline and 7-NI in its protective effect (p ! 0.05). In the surviving kits, JI-8 significantly improved the locomotion score over both saline and 7-NI scores. JI-8 was also significantly superior to saline in preserving smell, muscle tone and righting reflex function, but 7-NI did not show significant improvement. Furthermore, a 100-fold increase in the dose (15.75 mol/kg) of 7-NI significantly decreased systolic blood pressure in the dam, while JI-8 did not. The new class of inhibitors such as JI-8 shows promise in the prevention of cerebral palsy and is superior to the previously more commonly used nNOS inhibitor.

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Section: Discussionmentioning

confidence: 99%

Neuronal Nitric Oxide Synthase Inhibition Prevents Cerebral Palsy following Hypoxia-Ischemia in Fetal Rabbits: Comparison between JI-8 and 7-Nitroindazole

Derrick

Ji³

et al. 2011

Dev Neurosci

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“…Developmental trends in either of these parameters during fetal maturation could not be detected, probably due to an insufficient number of samples. An earlier report from our laboratory shows that fetal XOR activity decreases in the intestine, and increases in the liver towards term [11].…”

Section: Discussionmentioning

confidence: 99%

Xanthine Oxidoreductase Gene Expression and Enzyme Activity in Developing Human Tissues

Saksela

Lapatto

Raivio³

1998

Neonatology

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Xanthine oxidoreductase (XOR) has been implicated in tissue injury following ischemia-reperfusion because of its ability to generate reactive oxygen species under these conditions. In order to elucidate its role in various organs, we quantified the levels of XOR mRNA expression and activity in developing human tissues. XOR gene expression was highest in the intestine and in the liver, which also showed the highest enzyme activities. By a sensitive RNA-PCR assay, low levels of the transcript were detected in the kidney, lung, cardiac muscle, and brain of all subjects studied. XOR activities followed the mRNA distribution, being low or undetectable in tissues other than the liver and the intestine.

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“…Porém os radicais livres de oxigênio parecem atuar como mediadores da permeabilidade microvascular, principalmente por causa da associação com asfixia perinatal, a qual faz com que ocorra acúmulo de hipoxantina e propicia formação de radicais superóxido pela xantina oxidase, no intestino pós-isquêmico. Vettenranta et al 38 relataram quantidade substancial de xantina desidrogenase/oxidase no intestino fetal humano.…”

Section: -Retinopatia Da Prematuridadeunclassified

The importance of oxygen free radicals in the neonatal period

Rodrigues

1998

J Pediatr (Rio J)

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Objective: Oxygen free radicals are extremely reactive species and they can lead to injury and cell death. The aim of this review is to study the main biochemical aspects of free radical formation and their role as an intermediate mechanism of injury in several neonatal diseases.Methods: A brief history of oxygen therapy in neonatology and its relationship with complications associated with the production of free radicals. Definition, mechanism of action and antioxidant systems were described. Next, the neonatal factors of increased risk of free radical oxidative injury and the diseases associated with oxygen free radical toxicity were reviewed.Results: Oxygen free radicals are reactive species that although crucial to normal biological processes, can lead to injury and cell death. They are implicated in the pathogenesis of many neonatal diseases such as perinatal asphyxia, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, intracranial hemorrhage, pulmonary hypertension and persistence of ductus arteriosus. Birth is associated with transition to a hyperoxic environment in comparison with uterine environment, which leads to increased generation free radicals. The newborn has undeveloped antioxidant systems and, therefore, may be at increased risk of free radical oxidative injury.Conclusions: The understanding of neonatal factors involved in the pathogenesis of "oxygen free radical diseases" will lead to the development of new therapies for prevention and treatment of these neonatal diseases. J. pediatr. (Rio J.). 1998; 74(2):91-98: free radicals, oxygen, prematurity, antioxidants, newborn. ResumoObjetivos: Os radicais livres de oxigênio são espécies químicas altamente reativas, podendo levar à injúria e à morte celular. O objetivo desta revisão é analisar os principais aspectos da bioquími-ca da formação dos radicais livres e seu papel como mecanismo intermediário de lesão em diversas patologias no período neonatal.Métodos: Procedemos a um breve histórico sobre uso de oxigênio em neonatologia e suas complicações relacionadas à produção de radicais livres de oxigênio. Descrevemos sua definição e mecanismo de ação, bem como os mecanismos de defesa antioxidante. A seguir, revisamos as causas da propensão do neonato à injúria causada por essas espécies reativas tóxicas e as diversas patologias em que atuam como mecanismo patogênico.Resultados: Apesar de desempenhar um papel crucial nos precessos biológicos normais, os radicais livres de oxigênio são espécies químicas altamente reativas. Estão implicados na gênese de diversas patologias no período neonatal, tais como asfixia perinatal, broncodisplasia, enterite necrosante, hemorragia intracraniana, hipertensão pulmonar e persistência de canal arterial. O nascimento corresponde à transição para um ambiente com alta concentração de oxigênio comparado à vida intrauterina, o que leva a uma produção maior de radicais livres. O recém-nascido está mais suscetível à injúria oxidativa dessas espécies reativas tóxicas por ter uma defesa ...

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Xanthine Oxidase during Human Fetal Development

Cited by 27 publications

References 22 publications

Neuronal Nitric Oxide Synthase Inhibition Prevents Cerebral Palsy following Hypoxia-Ischemia in Fetal Rabbits: Comparison between JI-8 and 7-Nitroindazole

Neuronal Nitric Oxide Synthase Inhibition Prevents Cerebral Palsy following Hypoxia-Ischemia in Fetal Rabbits: Comparison between JI-8 and 7-Nitroindazole

Xanthine Oxidoreductase Gene Expression and Enzyme Activity in Developing Human Tissues

The importance of oxygen free radicals in the neonatal period

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