Oxidative changes in the rat brain by intraperitoneal injection of ferric nitrilotriacetate

Nakatsuka, Ichiro; Miyagawa, Shigeru; Andoh, Tsugunobu; Hayashi, Yusuke; Mizuno, Ryuichiro; Higuchi, Hitoshi; Miyawaki, Takuya

doi:10.1179/135100009x392575

Cited by 6 publications

(10 citation statements)

References 15 publications

(15 reference statements)

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“…Moreover, our data and others suggest that metal induced PD-like neurological dysfunction independently of the metal exposure route in vivo models [e.g. oral administration (this work), inhalation (Ordoñez-Librado et al 2010) or from aerosolized welding fumes (Sriram et al 2010), intra-peritoneal metal injection (Nakatsuka et al 2009) or intra-cranial metal injection (Ben-Shachar and Youdim 1991) in rats].…”

Section: Discussionmentioning

confidence: 86%

Acute and chronic metal exposure impairs locomotion activity in Drosophila melanogaster: a model to study Parkinsonism

2011

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The biometals iron (Fe), manganese (Mn) and copper (Cu) have been associated to Parkinson's disease (PD) and Parkinsonism. In this work, we report for the first time that acute (15 mM for up to 5 days) or chronic (0.5 mM for up to 15 days) Fe, Mn and Cu exposure significantly reduced life span and locomotor activity (i.e. climbing capabilities) in Drosophila melanogaster. It is shown that the concentration of those biometals dramatically increase in Drosophila's brain acutely or chronically fed with metal. We demonstrate that the metal accumulation in the fly's head is associated with the neurodegeneration of several dopaminergic neuronal clusters. Interestingly, it is found that the PPL2ab DAergic neuronal cluster was erode by the three metals in acute and chronic metal exposure and the PPL3 DAergic cluster was also erode by the three metals but in acute metal exposure only. Furthermore, we found that the chelator desferoxamine, ethylenediaminetetraacetic acid, and D: -penicillamine were able to protect but not rescue D. melanogaster against metal intoxication. Taken together these data suggest that iron, manganese and copper are capable to destroy DAergic neurons in the fly's brain, thereby impairing their movement capabilities. This work provides for the first time metal-induced Parkinson-like symptoms in D. melanogaster. Understanding therefore the effects of biometals in the Drosophila model may provide insights into the toxic effect of metal ions and more effective therapeutic approaches to Parkinsonism.

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Section: Discussionmentioning

confidence: 86%

Acute and chronic metal exposure impairs locomotion activity in Drosophila melanogaster: a model to study Parkinsonism

2011

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“…The few lines of evidence in mice show that HO-1 protein levels are increased in the brain of db/db mice and that this increase parallels the augmentation of isoprostanes and 8-OHdG, markers of lipid peroxidation and DNA oxidation, respectively [126]. Similarly, it was observed that the ferric nitrilotriacetate (Fe-NTA)-induced diabetes in rats was associated with an increase of HO-1 protein levels in the brain [127]. In addition, in another work, HO-1 mRNA expression in the brain of diabetic rats was unchanged with respect to the controls [128], thus leaving the information about HO-1 in the brain quite vague.…”

Section: Oxidative Stress: Is It the Driving Force For Insulin Resmentioning

confidence: 99%

Elevated risk of type 2 diabetes for development of Alzheimer disease: A key role for oxidative stress in brain

Butterfield

Domenico

Barone

2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

318

244

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Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Epidemiological data show that the incidence of AD increases with age and doubles every 5 years after 65 years of age. From a neuropathological point of view, amyloid-β-peptide (Aβ) leads to senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles and synapse loss, are the principal pathological hallmarks of AD. Aβ is associated with the formation of reactive oxygen (ROS) and nitrogen (RNS) species, and induces calcium-dependent excitotoxicity, impairment of cellular respiration, and alteration of synaptic functions associated with learning and memory. Oxidative stress was found to be associated with type 2 diabetes mellitus (T2DM), which (i) represents another prevalent disease associated with obesity and often aging, and (ii) is considered to be a risk factor for AD development. T2DM is characterized by high blood glucose levels resulting from increased hepatic glucose production, impaired insulin production and peripheral insulin resistance, which close resemble to the brain insulin resistance observed in AD patients. Furthermore, growing evidence suggest that oxidative stress play a pivotal role in the development of insulin resistance and vice versa. This review article provides molecular aspects and the pharmacological approaches from both preclinical and clinical data and interpreted from the point of view of oxidative stress with the aim to highlight progresses in this field.

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“…12 In this experiment, the changes appeared clearly by the direct injection of Fe-NTA into the brain. Surprisingly, the reaction of the mAChRs of the striatum was contrary to those of both the cortex and hippocampus.…”

Section: Discussionmentioning

confidence: 92%

“…15,16 In our previous report, the iron deposition was sparse, and the apoptotic change was not observed although oxidative change was induced. 12 Therefore, it is considered that oxidative mechanisms causing apoptosis were evoked by the iron from Fe-NTA injected into the brain in our study.…”

Section: Discussionmentioning

confidence: 99%

“…injection of Fe-NTA in rats. 12 In that study, the level of heme oxygenase (HO)-1 mRNA was raised, and lipid peroxidation was exaggerated, as well as changes in muscarinic acetylcholine receptors (mAChRs) in the brain. However, since iron accumulating in the brain was sparse, the effects of Fe-NTA in the brain are considered much weaker compared to those in peripheral organs such as the liver and kidneys after peripheral injection of Fe-NTA.…”

Section: Introductionmentioning

confidence: 97%

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Induction of apoptotic change in the rat hippocampus caused by ferric nitrilotriacetate

et al. 2011

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Iron, a source of oxidative stress, plays a major role in the pathology of neurodegenerative disease. In Alzheimer's disease, the hippocampus is vulnerable to oxidative stress, leading to impairment in memory formation. In our previous study, a brain oxidative reaction was induced after intraperitoneal injection of ferric nitrilotriacetate (Fe-NTA). However, since only a small amount of iron reached the brain in the previous study, Fe-NTA was administered into the hippocampus using an osmotic pump in this study. After continuous injection of Fe-NTA for 2 weeks, a high level of apoptotic change was induced in the hippocampus, in accordance with the iron localization. After injection for 4 weeks, the hippocampus was totally destroyed. A small amount of iron infiltrated into the cerebral cortex and the striatum, and deposition was observed at the choroid plexus and ependymal cells. However, no apoptotic reaction or clear tissue injury was observed in these areas. In addition, muscarinic acetylcholine receptors (M1, M2, and M4) were decreased in both the cortex and hippocampus while it increased in the striatum. Thus, the hippocampus is likely vulnerable to oxidative stress from Fe-NTA, and the oxidative stress is considered to bring the disturbance in the muscarinic acetylcholine receptors.

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Oxidative changes in the rat brain by intraperitoneal injection of ferric nitrilotriacetate

Cited by 6 publications

References 15 publications

Acute and chronic metal exposure impairs locomotion activity in Drosophila melanogaster: a model to study Parkinsonism

Acute and chronic metal exposure impairs locomotion activity in Drosophila melanogaster: a model to study Parkinsonism

Elevated risk of type 2 diabetes for development of Alzheimer disease: A key role for oxidative stress in brain

Induction of apoptotic change in the rat hippocampus caused by ferric nitrilotriacetate

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