Activation of arginine metabolism to glutamate in rat brain synaptosomes in thioacetamide‐induced hepatic encephalopathy: An adaptative response?

Albrecht, Jan; Hilgier, Wojciech; Rafałowska, Urszula

doi:10.1002/jnr.490250116

Cited by 35 publications

(18 citation statements)

References 24 publications

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“…By contrast, Arg uptake from blood to brain was found decreased in chronic HE (PCA) rats (Zanchin et al 1979) and in rats with thioacetamide (TAA)-induced HE (Albrecht et al 1996). With regard to Orn, increased brain uptake index of this amino acid coincident with its increased content in the blood was found in the TAA model of HE (Albrecht and Hilgier 1986; Albrecht et al 1994 1996; Albrecht et al 1996). Increased BBB transport of Orn in the TAA model has been considered as auto-protective response and in the same line has been speculated to facilitate intracerebral therapeutic action of the ammonia-trapping drug, l -ornithine- l -aspartate (LOLA) (Albrecht et al 1994; Albrecht et al 1996).…”

Section: Transcellular Passage Of Different Molecules Across the Endomentioning

confidence: 86%

“…With regard to Orn, increased brain uptake index of this amino acid coincident with its increased content in the blood was found in the TAA model of HE (Albrecht and Hilgier 1986; Albrecht et al 1994 1996; Albrecht et al 1996). Increased BBB transport of Orn in the TAA model has been considered as auto-protective response and in the same line has been speculated to facilitate intracerebral therapeutic action of the ammonia-trapping drug, l -ornithine- l -aspartate (LOLA) (Albrecht et al 1994; Albrecht et al 1996). However, the benefits of Orn may not apply to HE in a chronic setting, where blood to brain transport of Orn appears to remain unchanged (Zanchin et al 1979).…”

Section: Transcellular Passage Of Different Molecules Across the Endomentioning

confidence: 86%

“…Arg is a precursor of NO, a compound whose increased accumulation is engaged in the inflammatory response of the brain to ammonia (Jalan et al 2011), and in ammonia-induced brain swelling (Häussinger and Görg 2010), while decreased NO synthesis has been implicated in impairment of cognition associated with prolonged hyperammonemia (Felipo 2006). Moreover, HA increases Arg uptake to the different cell types within the CNS (Rao et al 1997; Hazell et al 1998), and HE in the TAA model stimulates Arg conversion to the neurotransmitter amino acids Glu and GABA as measured in the whole brain (Albrecht and Hilgier 1986) and in synaptosomes derived from these rats, which is likely to alter the balance between the inhibitory and excitatory neurotransmission (Albrecht et al 1990). Evaluation of the contribution of changes in Arg transport across the BBB to the availability of this amino acid in the brain cannot be accomplished without accounting for the variability in blood Arg content in the different hyperammonemic models.…”

Section: Transcellular Passage Of Different Molecules Across the Endomentioning

confidence: 99%

“…Similar to Arg, conversion of its product Orn to Glu/GABA is stimulated during HE (Albrecht and Hilgier 1986; Albrecht et al 1990). However, implications for this increased conversion for neurotransmission imbalance associated with HE are not known.…”

Section: Transcellular Passage Of Different Molecules Across the Endomentioning

confidence: 99%

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Alterations of Blood Brain Barrier Function in Hyperammonemia: An Overview

Skowrońska

Albrecht

2011

Neurotox Res

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Ammonia is a neurotoxin involved in the pathogenesis of neurological conditions associated with hyperammonemia, including hepatic encephalopathy, a condition associated with acute—(ALF) or chronic liver failure. This article reviews evidence that apart from directly affecting the metabolism and function of the central nervous system cells, ammonia influences the passage of different molecules across the blood brain barrier (BBB). A brief description is provided of the tight junctions, which couple adjacent cerebral capillary endothelial cells to each other to form the barrier. Ammonia modulates the transcellular passage of low-to medium-size molecules, by affecting their carriers located at the BBB. Ammonia induces interrelated aberrations of the transport of the large neutral amino acids and aromatic amino acids (AAA), whose influx is augmented by exchange with glutamine produced in the course of ammonia detoxification, and maybe also modulated by the extracellularly acting gamma-glutamyl moiety transferring enzyme, gamma-glutamyl-transpeptidase. Impaired AAA transport affects neurotransmission by altering intracerebral synthesis of catecholamines (serotonin and dopamine), and producing “false neurotransmitters” (octopamine and phenylethylamine). Ammonia also modulates BBB transport of the cationic amino acids: the nitric oxide precursor, arginine, and ornithine, which is an ammonia trap, and affects the transport of energy metabolites glucose and creatine. Moreover, ammonia acting either directly or in synergy with liver injury-derived inflammatory cytokines also evokes subtle increases of the transcellular passage of molecules of different size (BBB “leakage”), which appears to be responsible for the vasogenic component of cerebral edema associated with ALF.

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Section: Transcellular Passage Of Different Molecules Across the Endomentioning

confidence: 86%

Section: Transcellular Passage Of Different Molecules Across the Endomentioning

confidence: 86%

Section: Transcellular Passage Of Different Molecules Across the Endomentioning

confidence: 99%

Section: Transcellular Passage Of Different Molecules Across the Endomentioning

confidence: 99%

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Alterations of Blood Brain Barrier Function in Hyperammonemia: An Overview

Skowrońska

Albrecht

2011

Neurotox Res

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“…Thioacetamide, a selective hepatotoxin is well known as an inducer of hepatic failure within a short period of time after the administration of the drug [67]. It undergoes extensive metabolism to acetamide and thioacetamide S-dioxide by the mixed function oxidase system [68].…”

Section: Main Hepatotoxic Agents Used In Hepatoprotective Studiesmentioning

confidence: 99%

Hepatoprotective Effects of Mushrooms

et al. 2013

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Abstract:The particular characteristics of growth and development of mushrooms in nature result in the accumulation of a variety of secondary metabolites such as phenolic compounds, terpenes and steroids and essential cell wall components such as polysaccharides, β-glucans and proteins, several of them with biological activities. The present article outlines and discusses the available information about the protective effects of mushroom extracts against liver damage induced by exogenous compounds. Among mushrooms, Ganoderma lucidum is indubitably the most widely studied species. In this review, however, emphasis was given to studies using other mushrooms, especially those presenting efforts of attributing hepatoprotective activities to specific chemical components usually present in the mushroom extracts.

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Albrecht

1998

Journal of Neuroscience Research

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Many neurologic disorders are related to congenital or acquired hyperammonemia (HA). Advanced symptoms of HA range from seizures in acute stages to stupor and coma in more chronic conditions, manifesting variable imbalance between the inhibitory and excitatory neurotransmission. Evidence obtained with the use of experimental HA models suggests that acute neurotoxic effects of ammonia are mediated by overactivation of ionotropic glutamate (GLU) receptors, mainly the N-methyl-D-aspartate (NMDA) receptors, and to a lesser degree the KA/AMPA receptors. NMDA receptor-mediated neurotoxicity may be potentiated by impaired control of their function by metabotropic GLU receptors, which are inactivated by ammonia. Prolonged overactivation of the NMDA receptors upon extended ammonia exposure causes their downregulation. The GLU receptor changes may be related to their excessive exposure to extrasynaptic GLU. Ammonia promotes GLU accumulation in the extrasynaptic space by enhancing its release from neurons, and/or by decreasing its reuptake to the nerve endings and astrocytes, where the effect results from inactivation (downregulation) of the astrocytic glutamate transporter GLT1. Excitotoxic effects of ammonia are augmented by increased synthesis of nitric oxide (NO), which is associated with NMDA receptor activation and/or increased synaptic transport of arginine (ARG). A shift toward neural inhibition is promoted by positive modulation of the ␥-aminobutyric acid (GABA)ergic tone resulting from excessive accumulation in the brain of endogenous central benzodiazepine receptor agonists, and from upregulation of astrocytic peripheral benzodiazepine receptors leading to elevated levels of prognenelone-derived neurosteroids, which positively modulate the GABA(A) receptor complex. Inhibitory neurotransmission may also be favored by enhanced release from astrocytes of an inhibitory amino acid, taurine.

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Activation of arginine metabolism to glutamate in rat brain synaptosomes in thioacetamide‐induced hepatic encephalopathy: An adaptative response?

Cited by 35 publications

References 24 publications

Alterations of Blood Brain Barrier Function in Hyperammonemia: An Overview

Alterations of Blood Brain Barrier Function in Hyperammonemia: An Overview

Hepatoprotective Effects of Mushrooms

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