Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: Protective effect of folic acid

Matté, Cristiane; Mackedanz, Vanize; Stefanello, Francieli Moro; Scherer, Emilene B. S.; Andreazza, Ana Cristina; Zanotto, Caroline; Moro, Ângela M.; Garcia, Solange Cristina; Gonçalves, Carlos Alberto; Erdtmann, Bernardo; Salvador, Mirian; Wyse, Ângela T. S.

doi:10.1016/j.neuint.2008.08.011

Cited by 90 publications

(49 citation statements)

References 62 publications

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“…Numerous authors have reported that folic acid prevents oxidative stress induced by homocysteine both in central nervous and cardiovascular system (Singh et al 2011, Djuric et al 2007. Folic acid prevents reduction of antioxidant enzymes: catalase, glutathione peroxidase and superoxide dismutase in brain of hyperhomocysteinemic rats (Singh et al 2011, Matté et al 2009, and decreases the level of malondialdehyde (Singh et al 2011, Racek et al 2005 and superoxide anion (Djuric et al 2007). Finally, folic acid prevents inhibition of Na ?…”

Section: Discussionmentioning

confidence: 99%

Anticonvulsive Effect of Folic Acid in Homocysteine Thiolactone-Induced Seizures

et al. 2011

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Numerous studies have linked folate deficiency and resultant elevated plasma homocysteine levels with an increased risk of neurodegenerative diseases and seizures. The aim of the present study was to examine the effect of acute folic acid administration on behavioural and electroencephalographic (EEG) characteristics of DL homocysteine thiolactone-induced seizures in adult rats. Adult male Wistar rats were divided into following groups: (1) saline-treated (C); (2) DL homocysteine thiolactone 8 mmol/kg, i.p. (H); (3) groups that received folic acid i.p. in doses: 5 mg/kg (F(5)), 10 mg/kg (F(10)) and 15 mg/kg (F(15)) and (4) F 30 min prior to H (F(5)H, F(10)H and F(15)H, respectively). Seizure behaviour was assessed by incidence, latency, number and intensity of seizure episodes. Seizure severity was described by a descriptive scale with grades 0-4. For EEG recordings, under pentobarbital anaesthesia three gold-plated recording electrodes were implanted into the skull. There were no behavioural and EEG signs of seizure activity in C, F(5), F(10) and F(15) groups. In F(15)H group, the incidence of seizures was significantly lower, and the latency significantly prolonged, comparing to the H. Pre-treatment with F did not affect median number and severity of seizure episodes in all FH groups. Administration of F decreased mean total spectral power density in all FH groups, in a dose-dependent manner, in comparison with H. Our findings suggest that folic acid has anticonvulsive and antiepileptic effect on H-induced seizures in adult rats.

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Section: Discussionmentioning

confidence: 99%

Anticonvulsive Effect of Folic Acid in Homocysteine Thiolactone-Induced Seizures

et al. 2011

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“…Additionally, ectopic administration of homocysteine in the brain has been shown to enhance neuronal degeneration (21), likely due to the effect of elevated levels of homocysteine causing an accumulation of neuronal DNA damage (22). On a molecular level, increased homocysteine can cause a deficiency of methyl donors, which may result in misincorporation of uracil and oxidative damage to DNA bases (23).…”

Section: Discussionmentioning

confidence: 99%

A proteomics study of hyperhomocysteinemia injury of the hippocampal neurons using iTRAQ

Fang

Wang

Yan

et al. 2014

Molecular Medicine Reports

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Abstract. High levels of homocysteine, caused by abnormal methionine metabolism, can induce degeneration of mouse hippocampal neurons. iTRAQ™ technology has been widely used in the field of proteomics research and through employing this technology, the present study identified that hyperhomocysteinemia induced the downregulation of 52 proteins and upregulation of 44 proteins in the mouse hippocampus. Through gene ontology and pathway analysis, the upregulation of components of the cytoskeleton, actin, regulators of focal adhesion, calcium signaling pathways, tight junctions, ErbB and gonadotrophin-releasing hormone signaling, leukocyte, transendothelial migration, propanoate and pyruvate metabolism, valine, leucine and isoleucine biosynthesis, synthesis and degradation of ketone bodies and benzoate degradation via CoA ligation pathway, was identified. It was additionally verified that tau protein was highly expressed in the hyperhomocysteinemic neurons. Further analysis revealed that tau network proteins played functional roles in homocysteine-induced neuronal damage.

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“…Chronic hyperhomocysteinemia is associated with markers of oxidative damage and increased DNA damage in the parietal cortex and blood of rats. Concurrent administration of folic acid prevented these reported effects [246]. Furthermore, folate deprivation in neuronal cultures produces neurodegenerative changes characteristic to Alzheimer's disease, increased cytostolic calcium, increased ROS and decreased oxidative buffering capacity, accompanied by an increase in homocysteine [245].…”

Section: Neurotoxic Effectsmentioning

confidence: 99%

Nutritional modulation of cognitive function and mental health

Parletta

Milte

Meyer

2013

The Journal of Nutritional Biochemistry

245

187

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The important role of diet in cardiometabolic health is generally well recognised; for mental health, it is not so well understood. However, lifestyle risk factors for poor physical health are the same risk factors for mental illness, including poor diet. This is reflected by the high level of poor physical health in people with mental illness. Mediterranean, whole food diets have been associated with reduced risk for chronic disease, but very little research has investigated their mental health benefits. We provide a model for the pathways by which food components provided by a Mediterranean-style diet can facilitate healthy brain function. We then review evidence for the role of selected nutrients/food components -antioxidants, omega-3 fatty acids and B vitamins -in the brain and, hence, modulation of cognitive function and mental health. Converging evidence indicates multiple pathways by which these nutrients can assist in brain function, drawing from studies investigating them in isolation. There is very little work done on synergistic actions of nutrients and whole diets, highlighting a need for human intervention studies investigating benefits of Mediterranean-style diets for mental, as well as cardiometabolic health. ABSTRACTDietary risk factors for cardiometabolic health are generally well recognised; for mental

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Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: Protective effect of folic acid

Cited by 90 publications

References 62 publications

Anticonvulsive Effect of Folic Acid in Homocysteine Thiolactone-Induced Seizures

Anticonvulsive Effect of Folic Acid in Homocysteine Thiolactone-Induced Seizures

A proteomics study of hyperhomocysteinemia injury of the hippocampal neurons using iTRAQ

Nutritional modulation of cognitive function and mental health

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