Reactive nitrogen species mediate oxidative stress and astrogliosis provoked by in vivo administration of phytanic acid in cerebellum of adolescent rats: A potential contributing pathomechanism of cerebellar injury in peroxisomal disorders

Borges, Clarissa Günther; Canani, C.R.; Fernandes, Carolina Gonçalves; Zanatta, Ângela; Seminotti, Bianca; Ribeiro, César Augusto João; Leipnitz, Guilhian; Vargas, Carmen Regla

doi:10.1016/j.neuroscience.2015.07.028

Cited by 21 publications

(13 citation statements)

References 59 publications

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“…Particularly in the cerebellum, it can induce histopathological abnormalities, including Purkinje cells alteration with a cellular loss and delayed dendrite development and astrogliosis due to the disruption of redox homeostasis. Indeed, in a mouse model of Phyt intracerebellar administration reactive nitrogen species were increased [119], indicating the potential risks to cerebellar integrity.…”

Section: Postnatal Hyperoxiamentioning

confidence: 99%

Glial Factors Regulating White Matter Development and Pathologies of the Cerebellum

et al. 2020

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The cerebellum is a brain region that undergoes extremely dynamic growth during perinatal and postnatal development which is regulated by the proper interaction between glial cells and neurons with a complex concert of growth factors, chemokines, cytokines, neurotransmitters and transcriptions factors. The relevance of cerebellar functions for not only motor performance but also for cognition, emotion, memory and attention is increasingly being recognized and acknowledged. Since perturbed circuitry of cerebro-cerebellar trajectories can play a role in many central nervous system pathologies and thereby contribute to neurological symptoms in distinct neurodevelopmental and neurodegenerative diseases, is it the aim with this mini-review to highlight the pathways of glia-glia interplay being involved. The designs of future treatment strategies may hence be targeted to molecular pathways also playing a role in development and disease of the cerebellum.

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Section: Postnatal Hyperoxiamentioning

confidence: 99%

Glial Factors Regulating White Matter Development and Pathologies of the Cerebellum

et al. 2020

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“…The imbalance between the systemic production of reactive oxygen species (ROS) and the systemic capacity to quench and/or detoxify ROS production results in oxidative stress (1, 2). ROS can damage many cellular components, such as lipids, proteins, and nucleotides (3).…”

Section: Introductionmentioning

confidence: 99%

Lack of β, β‐carotene‐9′, 10′‐oxygenase 2 leads to hepatic mitochondrial dysfunction and cellular oxidative stress in mice

Guo

Hartson

et al. 2017

Molecular Nutrition Food Res

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Scope β,β-carotene-9’,10’-dioxygenase 2 (BCO2) is a carotenoid cleavage enzyme localized to the inner mitochondrial membrane in mammals. This study was aimed to assess the impact of genetic ablation of BCO2 on hepatic oxidative stress through mitochondrial function in mice. Methods and Results Liver samples from 6 week old male BCO2−/− knockout (KO) and isogenic wild-type (WT) mice were subjected to proteomics and functional activity assays. Compared to the WT, KO mice consumed more food (by 18 %) yet displayed significantly lower body weight (by 12 %). Mitochondrial proteomic results demonstrated that loss of BCO2 was associated with quantitative changes of the mitochondrial proteome mainly shown by suppressed expression of enzymes and/or proteins involved in fatty acid β–oxidation, the tricarboxylic acid cycle, and the electron transport chain (ETC). The mitochondrial basal respiratory rate, proton leak, and ETC complex II capacity were significantly elevated in the livers of KO compared to WT mice. Moreover, elevated reactive oxygen species and increased mitochondrial protein carbonylation were also demonstrated in liver of KO mice. Conclusions Loss of BCO2 induces mitochondrial hyperactivation, mitochondrial stress and changes of the mitochondrial proteome, leading to mitochondrial energy insufficiency. BCO2 appears to be critical for proper hepatic mitochondrial function.

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“…The total supernatant was used to determine enzymatic activities and protein oxidative damage. Protein content was measured using bovine serum albumin as standard ( Borges et al, 2015 ). Glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were determined according to Borges et al (2015) and peroxiredoxin (Prx) as previously described ( Kim et al, 2005 ).…”

Section: Methodsmentioning

confidence: 99%

“…Protein content was measured using bovine serum albumin as standard ( Borges et al, 2015 ). Glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were determined according to Borges et al (2015) and peroxiredoxin (Prx) as previously described ( Kim et al, 2005 ). Glucose-6-phosphate dehydrogenase (G6PD) activity was analyzed in a reaction mixture containing 10 mM MgCl 2 , 5 mM NADP + , 100 mM Tris HCl (pH 7.5) and approximately 3 μg of sample protein.…”

Section: Methodsmentioning

confidence: 99%

“…One unit (U) of G6PD corresponds to 1 mmol of substrate consumed per minute and the enzyme activity is expressed as U/mg protein ( Leong and Clark, 1984 ). Protein oxidative damage was assessed in liver supernatants by measuring carbonylated protein groups and sulfhydryl content as previously described ( Borges et al, 2015 ). Results were expressed as nmol/mg protein.…”

Section: Methodsmentioning

confidence: 99%

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Coenzyme Q10 or Creatine Counteract Pravastatin-Induced Liver Redox Changes in Hypercholesterolemic Mice

et al. 2018

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Statins are the preferred therapy to treat hypercholesterolemia. Their main action consists of inhibiting the cholesterol biosynthesis pathway. Previous studies report mitochondrial oxidative stress and membrane permeability transition (MPT) of several experimental models submitted to diverse statins treatments. The aim of the present study was to investigate whether chronic treatment with the hydrophilic pravastatin induces hepatotoxicity in LDL receptor knockout mice (LDLr-/-), a model for human familial hypercholesterolemia. We evaluated respiration and reactive oxygen production rates, cyclosporine-A sensitive mitochondrial calcium release, antioxidant enzyme activities in liver mitochondria or homogenates obtained from LDLr-/- mice treated with pravastatin for 3 months. We observed that pravastatin induced higher H2O2 production rate (40%), decreased activity of aconitase (28%), a superoxide-sensitive Krebs cycle enzyme, and increased susceptibility to Ca2+-induced MPT (32%) in liver mitochondria. Among several antioxidant enzymes, only glucose-6-phosphate dehydrogenase (G6PD) activity was increased (44%) in the liver of treated mice. Reduced glutathione content and reduced to oxidized glutathione ratio were increased in livers of pravastatin treated mice (1.5- and 2-fold, respectively). The presence of oxidized lipid species were detected in pravastatin group but protein oxidation markers (carbonyl and SH- groups) were not altered. Diet supplementation with the antioxidants CoQ10 or creatine fully reversed all pravastatin effects (reduced H2O2 generation, susceptibility to MPT and normalized aconitase and G6PD activity). Taken together, these results suggest that 1- pravastatin induces liver mitochondrial redox imbalance that may explain the hepatic side effects reported in a small number of patients, and 2- the co-treatment with safe antioxidants neutralize these side effects.

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Reactive nitrogen species mediate oxidative stress and astrogliosis provoked by in vivo administration of phytanic acid in cerebellum of adolescent rats: A potential contributing pathomechanism of cerebellar injury in peroxisomal disorders

Cited by 21 publications

References 59 publications

Glial Factors Regulating White Matter Development and Pathologies of the Cerebellum

Glial Factors Regulating White Matter Development and Pathologies of the Cerebellum

Lack of β, β‐carotene‐9′, 10′‐oxygenase 2 leads to hepatic mitochondrial dysfunction and cellular oxidative stress in mice

Coenzyme Q10 or Creatine Counteract Pravastatin-Induced Liver Redox Changes in Hypercholesterolemic Mice

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