N-Acetylcysteine Amide Exerts Possible Neuroprotective Effects in Newborn Pigs after Perinatal Asphyxia

Benterud, Torkil; Ystgaard, Martin Bogale; Manueldas, Sophia; Pankratov, Leonid; Alfaro-Cervelló, Clara; Florholmen, Geir; Ahmed, Mohammed S.; Sandvik, Leiv; Norgren, Svante; Bjørås, Magnar; Baumbusch, Lars Oliver; Solberg, Rønnaug; Saugstad, Ola Didrik

doi:10.1159/000447255

Cited by 7 publications

(9 citation statements)

References 38 publications

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“…Additional adjuvant strategies There are other treatments that have been tried out in addition to therapeutic hypothermia. These include noble gasses like Xenon and Argon, remote ischemic post-conditioning and the free-radical scavengers N-acetylcystein and N-acetylcystein amide [100][101][102][103][104][105] .…”

Section: Cannabinoidsmentioning

confidence: 99%

“…This was the first study that we know where DHA was administered in a large-animal model. We wanted to investigate the following in our well established piglet model: Preclinical models of hypoxic-ischemic injury involve a range from invitro studies of cell cultures 154 and brain slices 155 to animal models ranging from rodents 133,138 to larger lamb 156,157 and piglet models 59,89,103 and even to non-human primates 158 .…”

Section: Aims Of the Studymentioning

confidence: 99%

“…Anesthesia was maintained by a continuous infusion of fentanyl 50 μg/kg/hour and midazolam 0.25 mg/kg/h, yielding 1 ml/kg/hour for each drug. These modalities have been used extensively on newborn piglets in our research group 103,163,167,168 . The drugs have been thoroughly tested in newborn piglets 169,170 and we are aware of the alterations in cerebral blood flow that fentanyl 171 , phenobarbital 172 , and midazolam 173 exert.…”

Section: Anesthesia and Proceduresmentioning

confidence: 99%

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DHA reduces oxidative stress following hypoxia-ischemia in newborn piglets: a study of lipid peroxidation products in urine and plasma

Huun

Garberg

Escobar

et al. 2017

Journal of Perinatal Medicine

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Section: Cannabinoidsmentioning

confidence: 99%

Section: Aims Of the Studymentioning

confidence: 99%

Section: Anesthesia and Proceduresmentioning

confidence: 99%

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DHA reduces oxidative stress following hypoxia-ischemia in newborn piglets: a study of lipid peroxidation products in urine and plasma

Huun

Garberg

Escobar

et al. 2017

Journal of Perinatal Medicine

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“…Our group has recently described anti-inflammatory and possible neuroprotective effects of the antioxidant N-acetylcysteine amide (NACA) after neonatal hypoxia-reoxygenation in a neonatal pig model. Further, NACA reduced the levels of the proinflammatory cytokine IL-1 β and the transcription factor NF- κ B in the prefrontal cortex of the brain after neonatal hypoxia-reoxygenation [ 6 ]. The substance NACA has many similarities with N-acetylcysteine, which has been used as an antioxidant precursor to glutathione in the treatment of paracetamol overdose for more than 30 years [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Cerebellum Susceptibility to Neonatal Asphyxia: Possible Protective Effects of N-Acetylcysteine Amide

et al. 2018

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Background After perinatal asphyxia, the cerebellum presents more damage than previously suggested. Objectives To explore if the antioxidant N-acetylcysteine amide (NACA) could reduce cerebellar injury after hypoxia-reoxygenation in a neonatal pig model. Methods Twenty-four newborn pigs in two intervention groups were exposed to 8% oxygen and hypercapnia, until base excess fell to −20 mmol/l or the mean arterial blood pressure declined to <20 mmHg. After hypoxia, they received either NACA (NACA group, n = 12) or saline (vehicle-treated group, n = 12). One sham-operated group (n = 5) served as a control and was not subjected to hypoxia. Observation time after the end of hypoxia was 9.5 hours. Results The intranuclear proteolytic activity in Purkinje cells of asphyxiated vehicle-treated pigs was significantly higher than that in sham controls (p = 0.03). Treatment with NACA was associated with a trend to decreased intranuclear proteolytic activity (p = 0.08), There were significantly less mutations in the mtDNA of the NACA group compared with the vehicle-treated group, 2.0 × 10−4 (±2.0 × 10−4) versus 4.8 × 10−5(±3.6 × 10−4, p < 0.05). Conclusion We found a trend to lower proteolytic activity in the core of Purkinje cells and significantly reduced mutation rate of mtDNA in the NACA group, which may indicate a positive effect of NACA after neonatal hypoxia. Measuring the proteolytic activity in the nucleus of Purkinje cells could be used to assess the effect of different neuroprotective substances after perinatal asphyxia.

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“…Recently, we have published a study demonstrating that NACA displayed antiinflammatory properties after exposure to oxidative stress in an established neonatal piglet model, imitating perinatal asphyxia [2]. Our piglet model has been established for many years and several authors have shown a significant increase in markers of oxidative stress after the inflicted asphyxia [3].…”

Section: Introductionmentioning

confidence: 97%

N-Acetylcysteine Amide (NACA) Reduces Cell Death after Oxidative Stress in a Porcine Embryonic Kidney Cell Line

Benterud¹,

Manueldas²,

Norgren³

et al. 2017

JBiSE

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Introduction: Oxidative stress may have detrimental effects on different structures of the cells, such as the DNA. Recently, we have published a study demonstrating that N-Acetylcysteine amide (NACA) displayed anti-inflammatory properties on the brain after exposure to oxidative stress in an established neonatal piglet model, imitating perinatal asphyxia. As different clinical studies have shown an association between the severity of hypoxic-ischemic encephalopathy and damage of the kidneys, we investigated a possible protective effect of NACA against H 2 O 2-induced oxidative stress using a porcine epithelial-like embryonic kidney cell line (EFN-R). Objective: To investigate a potential protective effect of NACA on cells of a porcine embryonic kidney cell line exposed to H 2 O 2. Methods: We subjected the cells to different concentrations of H 2 O 2 for variable time periods, seeking the optimal dose-response for the experiments. Based on the results of these investigations, we exposed the cells to 100 μMol of H 2 O 2 and/or 750 μM of NACA for 24 hours. Some of the cells would receive NACA either one hour before or one hour after exposure to H 2 O 2. Results: The viability of the investigated EFN-R cells revealed that both, the group treated with NACA before exposure to H 2 O 2 and the group treated with NACA after exposure to H 2 O 2 , exhibited significantly higher cell viability compared to the H 2 O 2 group (p < 0.001 and p < 0.01, respectively). Discussion: The increased viability of the cells may indicate that NACA could play an important role in reducing oxidative stress. Taking the results from our previous study into consideration, our findings may streng

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N-Acetylcysteine Amide Exerts Possible Neuroprotective Effects in Newborn Pigs after Perinatal Asphyxia

Cited by 7 publications

References 38 publications

DHA reduces oxidative stress following hypoxia-ischemia in newborn piglets: a study of lipid peroxidation products in urine and plasma

DHA reduces oxidative stress following hypoxia-ischemia in newborn piglets: a study of lipid peroxidation products in urine and plasma

Cerebellum Susceptibility to Neonatal Asphyxia: Possible Protective Effects of N-Acetylcysteine Amide

N-Acetylcysteine Amide (NACA) Reduces Cell Death after Oxidative Stress in a Porcine Embryonic Kidney Cell Line

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