Vitamin C Prevents Intrauterine Programming of in vivo Cardiovascular Dysfunction in the Rat

Kane, Andrew D.; Herrera, Emílio; Camm, Emily J.; Giussani, Dino A.

doi:10.1253/circj.cj-13-0311

Cited by 63 publications

(84 citation statements)

References 64 publications

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“…However, it is possible that suppression of NO in the absence of injury could alter vascular tone and oxygen availability leading to ROS production and cell death in otherwise normal tissue. Such negative impacts of altered NO production in the absence of injury have been reported in rodent studies of antioxidant treatment using vitamin C [44][45][46]. As in the current study, these studies did include a no-injury group and reported vascular endothelial dysfunction later in life in offspring exposed to vitamin C in the absence of hypoxia [44][45][46].…”

Section: Potential Adverse Effects Of Wtapc Administration To Uninjursupporting

confidence: 62%

“…Such negative impacts of altered NO production in the absence of injury have been reported in rodent studies of antioxidant treatment using vitamin C [44][45][46]. As in the current study, these studies did include a no-injury group and reported vascular endothelial dysfunction later in life in offspring exposed to vitamin C in the absence of hypoxia [44][45][46]. Interestingly, wtAPC decreased astrogliosis in the corpus callosum and cortex irrespective of the mode of birth, despite the effect it had of increasing CD11β-positive and TUNEL-positive cell counts in the c-section controls.…”

Section: Potential Adverse Effects Of Wtapc Administration To Uninjurmentioning

confidence: 74%

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Evaluation of 3K3A-Activated Protein C to Treat Neonatal Hypoxic Ischemic Brain Injury in the Spiny Mouse

et al. 2019

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Neonatal hypoxic ischemic encephalopathy (HIE) resulting from intrapartum asphyxia is a global problem that causes severe disabilities and up to 1 million deaths annually. A variant form of activated protein C, 3K3A-APC, has cytoprotective properties that attenuate brain injury in models of adult stroke. In this study, we compared the ability of 3K3A-APC and APC (wild-type (wt)) to attenuate neonatal brain injury, using the spiny mouse (Acomys cahirinus) model of intrapartum asphyxia. Pups were delivered at 38 days of gestation (term = 39 days), with an intrapartum hypoxic insult of 7.5 min (intrapartum asphyxia cohort), or immediate removal from the uterus (control cohort). After 1 h, pups received a subcutaneous injection of 3K3A-APC or wild-type APC (wtAPC) at 7 mg/kg, or vehicle (saline). At 24 h of age, pups were killed and brain tissue was collected for measurement of inflammation and cell death using RT-qPCR and histopathology. Intrapartum asphyxia increased weight loss, inflammation, and apoptosis/necrosis in the newborn brain. 3K3A-APC administration maintained body weight and ameliorated an asphyxia-induced increase of TGFβ1 messenger RNA expression in the cerebral cortex, immune cell aggregation in the corpus callosum, and cell death in the deep gray matter and hippocampus. In the cortex, 3K3A-APC appeared to exacerbate the immune response to the hypoxic ischemic insult. While wtAPC reduced cell death in the corpus callosum and hippocampus following intrapartum asphyxia, it increased markers of neuro-inflammation and cell death in control pups. These findings suggest 3K3A-APC administration may be a useful therapy to reduce cell death and neonatal brain injury associated with HIE.

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Section: Potential Adverse Effects Of Wtapc Administration To Uninjursupporting

confidence: 62%

Section: Potential Adverse Effects Of Wtapc Administration To Uninjurmentioning

confidence: 74%

Evaluation of 3K3A-Activated Protein C to Treat Neonatal Hypoxic Ischemic Brain Injury in the Spiny Mouse

et al. 2019

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“…Several randomized controlled trials have been performed to determine whether antioxidants supplementation in complicated pregnancies are beneficial, showing no evidence that these supplements may prevent preeclampsia (Poston et al, 2006, 2011; Basaran et al, 2010; Roberts et al, 2010; Xu et al, 2010; Conde-Agudelo et al, 2011; Kalpdev et al, 2011; Rumbold et al, 2011; Polyzos et al, 2012). In marked contrast, animal models and few human experiences have shown effectiveness in the use of different antioxidants preventing pregnancy complications and short- and long-term vascular dysfunction during pathologic pregnancies (Richter et al, 2009; Tara et al, 2010; Parraguez et al, 2011; Giussani et al, 2012; Wibowo et al, 2012; Jones et al, 2013; Kane et al, 2013). Nowadays, it is not recommended the use of antioxidants in pregnancy but the debate is still open and it merits new therapeutical approaches as it is clear that oxidative stress is partly determining complications.…”

Section: Resultsmentioning

confidence: 99%

The placental pursuit for an adequate oxidant balance between the mother and the fetus

et al. 2014

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The placenta is the exchange organ that regulates metabolic processes between the mother and her developing fetus. The adequate function of this organ is clearly vital for a physiologic gestational process and a healthy baby as final outcome. The umbilico-placental vasculature has the capacity to respond to variations in the materno-fetal milieu. Depending on the intensity and the extensity of the insult, these responses may be immediate-, mediate-, and long-lasting, deriving in potential morphostructural and functional changes later in life. These adjustments usually compensate the initial insults, but occasionally may switch to long-lasting remodeling and dysfunctional processes, arising maladaptation. One of the most challenging conditions in modern perinatology is hypoxia and oxidative stress during development, both disorders occurring in high-altitude and in low-altitude placental insufficiency. Hypoxia and oxidative stress may induce endothelial dysfunction and thus, reduction in the perfusion of the placenta and restriction in the fetal growth and development. This Review will focus on placental responses to hypoxic conditions, usually related with high-altitude and placental insufficiency, deriving in oxidative stress and vascular disorders, altering fetal and maternal health. Although day-to-day clinical practice, basic and clinical research are clearly providing evidence of the severe impact of oxygen deficiency and oxidative stress establishment during pregnancy, further research on umbilical and placental vascular function under these conditions is badly needed to clarify the myriad of questions still unsettled.

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“…Studies have shown that treatment of offspring exposed to prenatal hypoxia with an antioxidant during prenatal or postnatal life prevented cardiac dysfunction (Kane et al . ) and cardiac susceptibility to I/R injury in adult life (Patterson et al . ).…”

Section: Discussionmentioning

confidence: 99%

Effect of resveratrol on metabolic and cardiovascular function in male and female adult offspring exposed to prenatal hypoxia and a high‐fat diet

Shah

Reyes

Morton

et al. 2015

The Journal of Physiology

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Key pointsr Prenatal hypoxia, a common outcome of many pregnancy complications, predisposes offspring to chronic diseases in later life.r We investigated the effect of prenatal hypoxia, on a background of a high-fat diet, on metabolic and cardiac function in adult male and female rat offspring. We also examined the therapeutic role of resveratrol supplementation in preventing metabolic and cardiac dysfunction.r Prenatal hypoxia impaired both metabolic and cardiac function in male and only cardiac function in female rat offspring. We also observed that male rat offspring were more susceptible to metabolic and cardiac dysfunction as compared with their female counterparts; this provides evidence of sexual dichotomy in the fetal programming of diseases due to prenatal hypoxia.r Resveratrol supplementation in the diet improved metabolic and cardiac function independent of sex; this provides evidence of a possible therapeutic role of resveratrol in susceptible male and female rat offspring exposed to prenatal hypoxia.Abstract Prenatal hypoxia, a common outcome of pregnancy complications, predisposes offspring to the development of metabolic and cardiovascular disorders in later life. We have previously observed that resveratrol improved cardiovascular and metabolic health in adult male rat offspring exposed to prenatal hypoxia and a postnatal high-fat (HF) diet; however, the effects of resveratrol in female rat offspring are not known. Our aim was to identify the mechanism(s) by which resveratrol may prevent metabolic and cardiac dysfunction in both male and female rat offspring exposed to prenatal hypoxia and a postnatal HF diet. Offspring that experienced normoxia or hypoxia in utero were fed a HF diet or a HF diet supplemented with resveratrol for 9 weeks following weaning. Body composition, metabolic function, in vivo cardiac function and ex vivo cardiac susceptibility to ischaemia-reperfusion (I/R) injury were assessed at 12 weeks of age. Prenatal hypoxia impaired metabolic function in male, but not female, rat offspring fed a HF diet and this was improved by resveratrol supplementation. Prenatal hypoxia also led to reduced recovery from cardiac I/R injury in male, and to a lesser extent in female, rat offspring fed a HF diet. Indices of cardiac oxidative stress after I/R were enhanced in both male and female rat offspring exposed to prenatal hypoxia. Resveratrol improved cardiac recovery from I/R injury and attenuated superoxide levels in both male and female rat offspring. In conclusion, prenatal hypoxia impaired metabolic and cardiac function in a sex-specific manner. Resveratrol supplementation may improve metabolic and cardiovascular health in adult male and female rat offspring exposed to prenatal hypoxia.

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Vitamin C Prevents Intrauterine Programming of in vivo Cardiovascular Dysfunction in the Rat

Cited by 63 publications

References 64 publications

Evaluation of 3K3A-Activated Protein C to Treat Neonatal Hypoxic Ischemic Brain Injury in the Spiny Mouse

Evaluation of 3K3A-Activated Protein C to Treat Neonatal Hypoxic Ischemic Brain Injury in the Spiny Mouse

The placental pursuit for an adequate oxidant balance between the mother and the fetus

Effect of resveratrol on metabolic and cardiovascular function in male and female adult offspring exposed to prenatal hypoxia and a high‐fat diet

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