Oxygen radicals: Common mediators of neurotoxicity

LeBel, Carl; Bondy, Stephen C.

doi:10.1016/0892-0362(91)90081-7

Cited by 148 publications

(72 citation statements)

References 66 publications

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“…Oxygen radicals and lipid peroxidation play a pivotal role in the observed damage during central nervous system trauma and stroke (70) (71), and more generally in neurotoxicity (72). Both oxygen radicals and peroxides are able to inactivate antioxidant enzymes (73).…”

Section: Pathophysiologic Relationship Of Lipid Peroxidation Productsmentioning

confidence: 99%

Lipid Peroxidation Products and Antioxidants in Human Disease

Romero¹,

Bosch‐Morell²,

Romero³

et al. 1998

Environmental Health Perspectives

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Lipid peroxidation (LPO) is a free radical-related process that in biologic systems may occur under enzymatic control, e.g., for the generation of lipid-derived inflammatory mediators, or nonenzymatically. This latter form is associated mostly with cellular damage as a result of oxidative stress, which also involves cellular antioxidants in this process. This article focuses on the relevance of two LPO products, malondialdehyde (MDA) and 4-hydroxynonenal (HNE), to the pathophysiology of human disease. The former has been studied in human serum samples of hepatitis C virus-infected adults and human immunodeficiency virus-infected children. In these two cases it is shown that the specific assay of serum MDA is useful for the clinical management of these patients. The presence of MDA in subretinal fluid of patients with retinal detachment suggests the involvement of oxidative stress in this process. Moreover, we were able to report the dependence of this involvement on the degree of myopia in these patients. The assay of MDA contents in the peripheral nerves of rats fed a chronic alcohol-containing diet or diabetic mice also confirms the pathophysiologic role of oxidative stress in these experimental models. In these two cases, associated with an increase in tissue LPO products content, we detected a decrease of glutathione peroxidase (GSHPx) activity in peripheral nerve, among other modifications. We have demonstrated that in vitro HNE is able to inhibit GSHPx activity in an apparent competitive manner, and that glutathione may partially protect and/or prevent this inactivation. The accumulation of LPO products in the brain of patients with Alzheimer's disease has also been described, and it is on the basis of this observation that we have tried to elucidate the role of oxidative stress and cellular antioxidants in ,B-amyloid-induced apoptotic cell death of rat embryo neurons. Finally, we discuss the possible role of the observed vascular effects of HNE on human arteries.

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Section: Pathophysiologic Relationship Of Lipid Peroxidation Productsmentioning

confidence: 99%

Lipid Peroxidation Products and Antioxidants in Human Disease

Romero¹,

Bosch‐Morell²,

Romero³

et al. 1998

Environmental Health Perspectives

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“…This influx of Ca 2+ is as a result of the phosphorylation processes of intracellular proteins, such as ion channels, receptors, enzymes, and transcription factors, which exhibit significant neuronal excitability and epileptic seizures (Butler et al, 1995). The release of free radicals has been implicated in many drug and chemical-induced toxicities (Lebel & Bondy, 1991). It is possible that increased production of reactive oxygen species could result to oxidant/anti-oxidant imbalance and thus, precipitate neurotoxicity (Gulati et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Anticonvulsant activity of aqueous fraction ofCarissa edulisroot bark

Ya’u

Yaro

Malami

et al. 2015

Pharmaceutical Biology

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Context: Carissa edulis Vahl (Apocynaceae) is used in Nigerian folk medicine to manage a plethora of diseases including epilepsy, cancer, and inflammation; its efficacy is widely acclaimed among communities of northern Nigeria. Objective: This study establishes anticonvulsant activities of aqueous fraction of ethanol root bark extract of Carissa edulis (RAF) and sub-fractions (S1 and S2) in animal models. Materials and methods:We evaluated the acute toxicity of the RAF, S1 and S2, and the anticonvulsant activity using pentylenetetrazole (PTZ), picrotoxin, strychnine, N-methyl-Daspartate (NMDA), isoniazid (INH), and aminophylline-induced seizures in mice. Their effects on maximal electroshock (MES) and kindling-induced seizures were studied in chicks and in rats, respectively, and in the electrophysiological study. The doses used for RAF were 150, 300, and 600 mg/kg while S1 and S2 were 250, 500, and 1000 mg/kg. Both RAF and sub-fractions were administered once during the experiment. Results: The intraperitoneal LD 50 of the RAF was estimated to be 2222.61 mg/kg and that of the S1 and S2 were above 5000 mg/kg. RAF protected the mice by 50% while sub-fractions by 16.67% against PTZ-induced seizures. RAF offered 33.33 and 16.67% protection against strychnine and NMDA models, respectively. However, RAF offered 66.67-33.33% protections against aminophylline-induced seizures at doses of 150 and 600 mg/kg, but RAF, S1, and S2 had no effect on MES-induced seizures. Discussion and conclusion: Our results validate the use of the plant traditionally in the management of epilepsy, thus supporting the appraisal of biologically active components of this plant as antiepileptic agents.

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“…1990), and inhibition of mitochondria (Hillered & Ernster, 1983). ROM also compromise blood-brain barrier functions (Greenwood, 1991), and act as mcdiators of neurotoxicity (LeBel & Bondy, 1991). However, in addition to their role in inducing pathological changes, age-related studies of superoxide dismutase (EC 1.15.1.1; SOD) show ROM involvement in foetal brain development, indicating a physiological function (Takashima et a/.…”

Section: B R a I N O X I D A T I V E Stressmentioning

confidence: 99%

Nutrient and toxin interactions in neurodegenerative disease

Evans

1994

Proc. Nutr. Soc.

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The brain is the most complex organ of the body. Its effective function is dependent on its unique anatomical structure and neuronal cell morphology, together with the efficient coordination of its metabolic and physiological processes. The degenerative diseases of the brain, for example Huntington's, Parkinson's and Alzheimer's disease (AD), are generally characterized by an associated loss of functional neurones, with accompanying motor, memory and cognitive deficits.In the case of familial amyotrophic lateral sclerosis (ALS; Deng et al. 1993), Huntington's disease, early-onset dementia of familial AD (Martin, 1993), and the prion diseases (the spongiform encephalopathies, i.e. Creutzfeldt-Jacob disease and the Gerstmann-Straussler-Scheinker syndrome; Prusiner, 1991), a genetic aetiology has been demonstrated. The larger number of so-called sporadic cases of AD which occur in the 8th and 9th decades of life, suggests that environmental factors are also operative. Even so, recent findings concerning apolipoprotein E €4 allele indicate genetic polymorphisms are significant risk factors in the development of late-onset AD as well . Hence, senile dementia of the Alzheimer type, the most common of the neurodegenerative diseases, appears to be of multifactorial origin, presenting a complex interplay of genetic, environmental, and age-related factors (Calne et al. 1986). B R A I N R E S E A R C HUndertaking studies into the toxicological and nutritional aspects of neurodegeneration, poses a range of ethical, organizational, technical and financial, challenges. Since there is no laboratory test for AD and the definitive diagnosis is dependent on postmortem identification and quantification of the pathognomic intracellular neurofibrillary tangles and extracellular senile plaques within the brain, epidemiological and clinical investigations into AD are extremely problematic. However, tests for cognitive function, and development of new in vivo imaging techniques, namely magnetic resonance imaging and positron emission topography scans, do permit a degree of clinical assessment.The inherent difficulty of research into the brain is compounded not only by the diverse range of neuronal and glial cell types and the complexity of the integrated neural network, but also by the properties of redundancy and plasticity exhibited by the brain. Brain damage related to degenerative change may not become apparent until the loss of neurones reaches a particular threshold level. Hence, cognitive deficits appearing in later life may not be directly caused by senility or the ageing process itself, but may be the result of developmental deficits or toxic damage which has occurred several decades earlier. Studies indicating the major significance of pre-or early postnatal nutrition to infant brain development (Lucas, 1993) and the subsequent development of disease in adult life (Barker et al. 1989), are of particular importance in relation to the nonreplicative nature of neuronal cells. While the significance of proper nutrition in early b...

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Oxygen radicals: Common mediators of neurotoxicity

Cited by 148 publications

References 66 publications

Lipid Peroxidation Products and Antioxidants in Human Disease

Lipid Peroxidation Products and Antioxidants in Human Disease

Anticonvulsant activity of aqueous fraction ofCarissa edulisroot bark

Nutrient and toxin interactions in neurodegenerative disease

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