Peroxidation of brain lipids in vitro: Nitric oxide versus hydroxyl radicals

Rauhala, Pekka; Sziráki, István; Chiueh, Chuang C.

doi:10.1016/0891-5849(96)00043-3

Cited by 42 publications

(31 citation statements)

References 10 publications

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“…• with lipid peroxyl radicals, thereby terminating the chain reaction of lipid peroxidation initiated by such reactive species as hydroxyl radical or peroxynitrite (Rauhala et al, 1996;Rubbo et al, 1994;Wink and Mitchell, 1998). Therefore, it is not possible to predict a priori whether a decrease in the expression of NOS (and, by inference, a decreased production of NO…”

Section: Pathophysiologic Actions Of Nitric Oxidementioning

confidence: 99%

Role of nitric oxide in the pathogenesis of muscular dystrophies: A “two hit” hypothesis of the cause of muscle necrosis

Rando

2001

Microscopy Res & Technique

121

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Although the genetic and biochemical bases of many of the muscular dystrophies have been elucidated, the pathophysiological mechanisms leading to muscle cell death and degeneration remain elusive. Among the most well studied of the dystrophies are those due to defects in proteins that make up the dystrophin-glycoprotein complex (DGC). There has been much interest in the role of nitric oxide (NO(*)) in the pathogenesis of these diseases because the enzyme that synthesizes NO(*), nitric oxide synthase (NOS), is associated with the DGC. Recent studies of dystrophies related to DGC defects suggest that one mechanism of cellular injury is functional ischemia related to alterations in cellular NOS and disruption of a normal protective action of NO(*). This protective action is the prevention of local ischemia during contraction-induced increases in sympathetic vasoconstriction. However, the loss of this protection, alone, does not explain the subsequent muscle cell death and degeneration since mice lacking neuronal NOS (the predominant isoform expressed in muscle) do not develop a muscular dystrophy. Thus, there must be additional biochemical changes conferred upon the cells by these DGC defects, and these changes are discussed in terms of a proposed "two hit" hypothesis of the pathogenetic mechanisms that underlie the muscular dystrophies. According to this hypothesis, pathogenic defects in the DGC have at least two biochemical consequences: a reduction in NO(*)-mediated protection against ischemia, and an increase in cellular susceptibility to metabolic stress. Either one alone may be insufficient to lead to muscle cell death. However, in combination, the biochemical consequences are sufficient to cause muscle degeneration. The role of oxidative stress as a final common pathophysiologic pathway is discussed in terms of data showing that oxidative injury precedes pathologic changes and that muscle cells with defects in the DGC have an increased susceptibility to oxidant challenges. Accordingly, this "two hit" hypothesis may explain many of the complex spatial and temporal variations in disease expression that characterize the muscular dystrophies, such as grouped necrosis, a pre-necrotic phase of the disease, and selective muscle involvement.

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Section: Pathophysiologic Actions Of Nitric Oxidementioning

confidence: 99%

Role of nitric oxide in the pathogenesis of muscular dystrophies: A “two hit” hypothesis of the cause of muscle necrosis

Rando

2001

Microscopy Res & Technique

121

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“…The possible "crosstalk" between RNS (NO ~ and its derivatives) and ROS (O2-, ~ and H202) should attract research interest in the next century. Now it is clear, that any deliberation about the in vivo unavoidable generation and actions of RNS (Table II) could not be performed without taking into account the evident contribution of ROS (reactions 1-39) (Chiueh, 1994;Halliwell 1996;Menconi et al, 1998;Rauhala et al, 1996;Wennmalm et al, 1994). However, the ratio RNS/ROS may be all of vital importance as it was suggested before (Halliwell, 1992).…”

Section: Reactive Nitrogen Species (Rns)mentioning

confidence: 99%

Reactive oxygen species and reactive nitrogen species: Relevance to cyto(neuro)toxic events and neurologic disorders. An overview

1999

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Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed under physiological conditions in the human body and are removed by cellular antioxidant defense systems. During oxidative stress their increased formation leads to tissue damage and cell death. This process may be especially important in the central nervous system (CNS) which is vulnerable to ROS and RNS damage as the result of high 02 consumption, high lipid content and the relatively low antioxidant defenses in brain, compared with other tissues.Recently there has been an increased number of reports suggesting the involvement of free radicals and their non-radical derivatives in a variety of pathological events and multistage disorders including neurotoxicity, apoptotic death of neurons, and neural disorders: Alzheimer's (AD), Parkinson's disease (PD) and schizophrenia. Taking into consideration the basic molecular chemistry of ROS and RNS, their overall generation and location, in order to control or supress their action it is essential to understand the fundamental aspects of this problem. In this presentation we review and summarize the basics of all the recently known and important properties, mechanisms, molecular targets, possible involvement in cellular (neural) degeneration and apoptotic death and in pathogenesis of AD, PD and schizophrenia.The aim of this article is to provide an overview of our current knowledge of this problem and to inspire experimental strategies for the evaluation of optimum innovative therapeutic trials. Another purpose of this work is to shed some light on one of the most exciting recent advances in our understanding of the CNS: the realisation that RNS pathway is highly relevant to normal brain metabolism and to neurologic disorders as well. The interactions of RNS and ROS, their interconversions and the ratio of RNS/ ROS could be an important neural tissue injury mechanism(s) involved into etiology and pathogenesis of AD, PD and schizophrenia.It might be possible to direct therapeutic efforts at oxidative events in the pathway of neuronal degeneration and apoptotic death. From reviewed data, no single substance can be recommended for use in human studies. Some of the recent therapeutic strategies and neuroprotective trials need further development particularly those of antioxidants enhancement. Such an approach should also consider using combinations of radical(s) scavengers rather than a single substance.

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“…These findings are supported by the results of the present study that the inhibition of nNOS significantly decreased iron-induced hippocampal cell loss. However, several studies have suggested protective effects of NO on iron-induced neurotoxicity (Rauhala et al 1996;Lin 1999). Conflicting results probably depend on the differences in the neurotoxic agents, the part of brain investigated, the application ways of substances regarding NO system, the given doses, and the experimental methods.…”

Section: Discussionmentioning

confidence: 99%

“…NO is one of the substances that involved in iron-induced cell death (Rauhala et al 1996;Lin 1999). Some studies found that NO is a neuroprotective substance (Verrecchia et al 1995;Lin 1999), while others qualify it as neurotoxic (Gokce et al 2003;Danielisova et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Neuroprotection by 7-Nitroindazole Against Iron-Induced Hippocampal Neurotoxicity

Bostanci

Bağirici

2007

Cell Mol Neurobiol

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(1) Iron plays an important role in maintaining normal brain function. In some neurodegenerative disorders including Parkinson's and Alzheimer's disease, iron levels rise in the brain. It is known that higher iron levels induce neuronal hyperactivity and oxidative stress. A body of evidence indicates a relationship between neuronal death and nitric oxide (NO). The aim of present study was to evaluate the effects of NO produced by neuronal nitric oxide synthase (nNOS) on iron-induced neuronal death. (2) Animals were classified into four groups: control, iron, iron+7-nitroindazole, and iron+vehicle. Rats in iron, iron+7-nitroindazole, and iron+vehicle groups received intracerebroventricular (i.c.v.) FeCl3 injection (200 mM, in 2.5 microl). Rats belonging to control groups received the same amount of saline into the cerebral ventricles. All animals were kept alive for 10 days following the operation. Animals in iron+7-nitroindazole group received intraperitoneal 7-nitroindazole (30 mg/kg/day) injections once a day during this period, while the rats belonging to vehicle group received daily intraperitoneal injection of peanut oil. After 10 days, rats were perfused intracardially under deep urethane anesthesia. Removed brains were processed using the standard histological techniques. (3) The total number of neurons in hippocampus of all rats was estimated with the unbiased stereological techniques. Results of present study show that 7-nitroindazole decreased mean neuron loss from 43% to 11%. Treatment of peanut oil alone did not affect iron-induced hippocampal cell loss with respect to iron group values. (4) Findings of our study suggest that 7-nitroindazole may have neuroprotective effects against iron-induced hippocampal neurotoxicity by inhibiting nNOS.

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Peroxidation of brain lipids in vitro: Nitric oxide versus hydroxyl radicals

Cited by 42 publications

References 10 publications

Role of nitric oxide in the pathogenesis of muscular dystrophies: A “two hit” hypothesis of the cause of muscle necrosis

Role of nitric oxide in the pathogenesis of muscular dystrophies: A “two hit” hypothesis of the cause of muscle necrosis

Reactive oxygen species and reactive nitrogen species: Relevance to cyto(neuro)toxic events and neurologic disorders. An overview

Neuroprotection by 7-Nitroindazole Against Iron-Induced Hippocampal Neurotoxicity

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