2010
DOI: 10.1097/mco.0b013e328333b829
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Interaction of oxidative stress, astrocyte swelling and cerebral ammonia toxicity

Abstract: Oxidative/nitrosative stress and a low-grade cerebral edema as key events in the pathogenesis of ammonia toxicity and hepatic encephalopathy may offer potential new strategies for treatment. Ammonia-induced oxidation of RNA and proteins may impair postsynaptic protein synthesis, which is critically involved in learning and memory consolidation. RNA oxidation offers a novel explanation for multiple disturbances of neurotransmitter systems and gene expression and the cognitive deficits observed in hepatic enceph… Show more

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Cited by 117 publications
(156 citation statements)
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References 75 publications
(123 reference statements)
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“…Excessive ammonia concentrations are toxic particularly to the brain and impaired ammonia detoxification by the liver is a major cause of hepatic encephalopathy. [45][46][47] Apparently, toxic ammonia concentrations have not been reached by the treatment, because the treated mice lived an almost normal life span in contrast with the severe reduction of life span in untreated mice. Moreover, long-term treatment of wild-type mice did not lead to obvious alterations of behavior.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Excessive ammonia concentrations are toxic particularly to the brain and impaired ammonia detoxification by the liver is a major cause of hepatic encephalopathy. [45][46][47] Apparently, toxic ammonia concentrations have not been reached by the treatment, because the treated mice lived an almost normal life span in contrast with the severe reduction of life span in untreated mice. Moreover, long-term treatment of wild-type mice did not lead to obvious alterations of behavior.…”
Section: Discussionmentioning
confidence: 99%
“…43 As a result, NH 4 Cl alkalinizes acidic cellular compartments 44 and swells cells. [45][46][47] Cell swelling downregulates the cell volume-sensitive transcription factor Tonicity-Responsive Enhancer Binding Protein or nuclear factor of activated T cells (NFAT5), 48,49 which has been implicated in the regulation of Cbfa1 expression, a function involving the transcription factor Sox9. 50 Beyond that, lysosomal alkalinization prevents maturation of several proteins including TGFB1, 51 which in turn is known to upregulate NFAT5 52 and participate in osteogenic signaling.…”
mentioning
confidence: 99%
“…In the present study, GSH was remarkably decreased by TAA both in liver (Al-Attar, 2012; Amin et al, 2012) and brain (Singh et al, 2014) of MHE rats. The increased production of reactive oxygen and nitrogen oxide species (ROS/RNOS) in the brain cells, in turn, is likely to amplify the neuronal derangements associated with HE pathogenesis (Haussinger and Gorg, 2010). Moreover, results demonstrated significant elevation in LP during TAA-induced HE in liver and brain.…”
Section: Resultsmentioning
confidence: 98%
“…Ammonium (NH 4 + and ammonia (NH 3 ) are considered the primary toxins responsible for the functional deficits observed in HE, the treatment of which is based primarily on reducing blood and brain NH 4 + /NH 3 concentrations. The arterial concentration of NH 4 + /NH 3 in HE patients and HE animal models is increased, and predicts the severity of the symptoms [1].…”
Section: Ammonium's Central Rolementioning
confidence: 99%
“…The intracellular accumulation of glutamine contributes to astrocytic swelling, which is counteracted by release of osmolytes such as myoinositol and taurine. Astrocytic swelling leads to production of reactive oxygen and nitrogen compounds, which in turn exacerbate the swelling [4]. In the case of acute HE, astrocyte swelling affects both the cell bodies and their branches and may be so extensive that the fatal cerebral oedema mentioned above ensues [1].…”
mentioning
confidence: 99%