scholarly journals S-Adenosylmethionine Deficiency and Brain Accumulation of S-Adenosylhomocysteine in Thioacetamide-Induced Acute Liver Failure

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2135
Author(s):  
Anna Maria Czarnecka ◽  
Wojciech Hilgier ◽  
Magdalena Zielińska
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Redox Homeostasis ◽  
Cerebral Function ◽  
Total Glutathione ◽  
Cellular Redox ◽  
Therapeutic Value ◽  
Transsulfuration Pathway ◽  
Subsequent Hydrolysis ◽  
The Brain

Background: Acute liver failure (ALF) impairs cerebral function and induces hepatic encephalopathy (HE) due to the accumulation of neurotoxic and neuroactive substances in the brain. Cerebral oxidative stress (OS), under control of the glutathione-based defense system, contributes to the HE pathogenesis. Glutathione synthesis is regulated by cysteine synthesized from homocysteine via the transsulfuration pathway present in the brain. The transsulfuration-transmethylation interdependence is controlled by a methyl group donor, S-adenosylmethionine (AdoMet) conversion to S-adenosylhomocysteine (AdoHcy), whose removal by subsequent hydrolysis to homocysteine counteract AdoHcy accumulation-induced OS and excitotoxicity. Methods: Rats received three consecutive intraperitoneal injections of thioacetamide (TAA) at 24 h intervals. We measured AdoMet and AdoHcy concentrations by HPLC-FD, glutathione (GSH/GSSG) ratio (Quantification kit). Results: AdoMet/AdoHcy ratio was reduced in the brain but not in the liver. The total glutathione level and GSH/GSSG ratio, decreased in TAA rats, were restored by AdoMet treatment. Conclusion: Data indicate that disturbance of redox homeostasis caused by AdoHcy in the TAA rat brain may represent a deleterious mechanism of brain damage in HE. The correction of the GSH/GSSG ratio following AdoMet administration indicates its therapeutic value in maintaining cellular redox potential in the cerebral cortex of ALF rats.

scholarly journals Wilson Disease-Induced Acute Liver Failure (NWI = 13) Salvaged without Liver Transplant by Plasmapheresis

2021 ◽  
Vol 11 (01) ◽  
pp. e145-e147
Author(s):  
Nida Mirza ◽  
Ravi Bharadwaj ◽  
Smita Malhotra ◽  
Anupam Sibal
Keyword(s):  
Liver Transplantation ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Wilson Disease ◽  
Prognostic Score ◽  
Prognostic Index ◽  
Kidney Injury ◽  
Copper Metabolism ◽  
Life Saving ◽  
The Brain

AbstractWilson disease (WD) is a disorder of copper metabolism resulting in accumulation of copper in vital organs of the human body, predominantly in the liver and the brain. Acute liver failure in WD has a bad prognosis, especially with a score ≥11 in the revised WD prognostic index; emergency liver transplantation is considered the only life-saving option in this scenario. Here, we reported a girl patient with WD-induced liver failure and poor prognostic score who was rescued by plasmapheresis. She also manifested severe Coombs negative hemolytic anemia and acute kidney injury. This case report highlights the utility of an adjunctive modality besides liver transplantation for the management of fulminant liver failure caused by WD.

scholarly journals Glutamine synthetase expression in the brain during experimental acute liver failure (immunohistochemical study)

2021 ◽  
Vol 11 (10) ◽  
pp. 342-356
Author(s):  
T. Shulyatnikova ◽  
V. Tumanskiy
Keyword(s):  
White Matter ◽  
Glutamine Synthetase ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Caudate Nucleus ◽  
Immunohistochemical Study ◽  
Clinical Signs ◽  
Brain Regions ◽  
Progressive Increase ◽  
The Brain

The aim of the study was to determine the immunohistochemical level of glutamine synthetase (GS) expression in different brain regions in the conditions of experimental acute liver failure in rats. Materials and methods. The study was conducted in Wistar rats: 5 sham (control) animals and 10 rats with acetaminophen induced liver failure model (AILF). The immunohistochemical study of GS expression in the sensorimotor cortex, white matter, hippocampus, thalamus, caudate nucleus/putamen was carried out in the period of 12-24 h after acetaminophen treatment. Results. Beginning from the 6th hour after acetaminophen treatment all AILF-animals showed the progressive increase in clinical signs of acute brain disfunction finished in 6 rats by comatose state up to 24 h - they constituted subgroup AILF-B, “non-survived”. 4 animals survived until the 24 h - subgroup AILF-A, “survived”. In the AILF-B group, starting from 16 to 24 hours after treatment, a significant (relative to control) regionally-specific dynamic increase in the level of GS expression was observed in the brain: in the cortex – by 307.33 %, in the thalamus – by 249.47%, in the hippocampus – by 245.53%, in the subcortical white matter – by 126.08%, from 12th hour – in the caudate nucleus/putamen, by 191.66 %; with the most substantive elevation of GS expression in the cortex: by 4.07 times. Conclusion. Starting from the 16th hours after the acetaminophen treatment (from the 12th h in the caudate nucleus/putamen region) and up to 24 h, it is observed reliable compared to control dynamic increase in GS protein expression in the cortex, white matter, hippocampus, thalamus, caudate nucleus/putamen of the rat brain with the most significant elevation in the cortex among other regions. The heterogeneity in the degree of GS expression rising in different brain regions potentially may indicate regions more permeable for ammonia and/or other systemic toxic factors as well as heterogeneous sensitivity of brain regions to deleterious agents in conditions of AILF. Subsequently, revealed diversity in the GS expression reflects the specificity of reactive response of local astroglia in the condition of AILF-encephalopathy during specific time-period. The dynamic increase in the GS expression associated with impairment of animal state, indicates involvement of increased GS levels in the mechanisms of experimental acute hepatic encephalopathy.

scholarly journals Quantitative multivoxel 1H MR spectroscopy of the brain in children with acute liver failure

2008 ◽  
Vol 18 (11) ◽  
pp. 2601-2609 ◽  
Author(s):  
Paul E. Sijens ◽  
Heyder Alkefaji ◽  
Roelineke J. Lunsing ◽  
Francjan J. van Spronsen ◽  
Linda C. Meiners ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Mr Spectroscopy ◽  
1H Mr Spectroscopy ◽  
The Brain

Subchronic treatment with acai frozen pulp prevents the brain oxidative damage in rats with acute liver failure

2016 ◽  
Vol 31 (6) ◽  
pp. 1427-1434 ◽  
Author(s):  
Fernanda de Souza Machado ◽  
Jonnsin Kuo ◽  
Mariane Farias Wohlenberg ◽  
Marina da Rocha Frusciante ◽  
Márcia Freitas ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Subchronic Treatment ◽  
The Brain

scholarly journals NMR study of 13C-glucose and 13C-acetate metabolism in the brain of rats with acute liver failure

2008 ◽  
Vol 81 ◽  
pp. 9-13
Author(s):  
C. Zwingmann ◽  
N. Chatauret ◽  
D. Leibfritz ◽  
R. F. Butterworth
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Acetate Metabolism ◽  
Nmr Study ◽  
The Brain

The Na–K–Cl cotransporter in the brain edema of acute liver failure

2011 ◽  
Vol 54 (2) ◽  
pp. 272-278 ◽  
Author(s):  
Arumugam R. Jayakumar ◽  
Vanessa Valdes ◽  
Michael D. Norenberg
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Brain Edema ◽  
The Brain

Allopurinol Ameliorates Thioacetamide-Induced Acute Liver Failure by Regulating Cellular Redox-Sensitive Transcription Factors in Rats

Inflammation ◽  
2012 ◽  
Vol 35 (4) ◽  
pp. 1549-1557 ◽  
Author(s):  
Ulvi Demirel ◽  
Mehmet Yalnız ◽  
Cem Aygün ◽  
Cemal Orhan ◽  
Mehmet Tuzcu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Cellular Redox

scholarly journals A Clinically Relevant Variant of the Human Hydrogen Sulfide-Synthesizing Enzyme Cystathionineβ-Synthase: Increased CO Reactivity as a Novel Molecular Mechanism of Pathogenicity?

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
João B. Vicente ◽  
Henrique G. Colaço ◽  
Francesca Malagrinò ◽  
Paulo E. Santo ◽  
André Gutierres ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Redox Homeostasis ◽  
Crystallographic Structure ◽  
Wild Type ◽  
Gene Encoding ◽  
Cellular Redox ◽  
Transsulfuration Pathway ◽  
Key Enzyme ◽  
A Minor ◽  
Ferrous Heme

The human disease classical homocystinuria results from mutations in the gene encoding the pyridoxal 5′-phosphate- (PLP-) dependent cystathionineβ-synthase (CBS), a key enzyme in the transsulfuration pathway that controls homocysteine levels, and is a major source of the signaling molecule hydrogen sulfide (H2S). CBS activity, contributing to cellular redox homeostasis, is positively regulated byS-adenosyl-L-methionine (AdoMet) but fully inhibited upon CO or NO• binding to a noncatalytic heme moiety. Despite extensive studies, the molecular basis of several pathogenicCBSmutations is not yet fully understood. Here we found that the ferrous heme of the reportedly mild p.P49L CBS variant has altered spectral properties and markedly increased affinity for CO, making the protein much more prone than wild type (WT) CBS to inactivation at physiological CO levels. The higher CO affinity could result from the slightly higher flexibility in the heme surroundings revealed by solving at 2.80-Å resolution the crystallographic structure of a truncated p.P49L. Additionally, we report that p.P49L displays impaired H2S-generating activity, fully rescued by PLP supplementation along the purification, despite a minor responsiveness to AdoMet. Altogether, the results highlight how increased propensity to CO inactivation of an otherwise WT-like variant may represent a novel pathogenic mechanism in classical homocystinuria.

scholarly journals Redox Homeostasis and Prospects for Therapeutic Targeting in Neurodegenerative Disorders

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Musbau Adewumi Akanji ◽  
Damilare Emmanuel Rotimi ◽  
Tobiloba Christiana Elebiyo ◽  
Oluwakemi Josephine Awakan ◽  
Oluyomi Stephen Adeyemi
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Redox Homeostasis ◽  
Reactive Species ◽  
Cellular Damage ◽  
Cellular Mechanisms ◽  
Cellular Redox ◽  
Redox Imbalance ◽  
Cellular Processes ◽  
The Brain

Reactive species, such as those of oxygen, nitrogen, and sulfur, are considered part of normal cellular metabolism and play significant roles that can impact several signaling processes in ways that lead to either cellular sustenance, protection, or damage. Cellular redox processes involve a balance in the production of reactive species (RS) and their removal because redox imbalance may facilitate oxidative damage. Physiologically, redox homeostasis is essential for the maintenance of many cellular processes. RS may serve as signaling molecules or cause oxidative cellular damage depending on the delicate equilibrium between RS production and their efficient removal through the use of enzymatic or nonenzymatic cellular mechanisms. Moreover, accumulating evidence suggests that redox imbalance plays a significant role in the progression of several neurodegenerative diseases. For example, studies have shown that redox imbalance in the brain mediates neurodegeneration and alters normal cytoprotective responses to stress. Therefore, this review describes redox homeostasis in neurodegenerative diseases with a focus on Alzheimer’s and Parkinson’s disease. A clearer understanding of the redox-regulated processes in neurodegenerative disorders may afford opportunities for newer therapeutic strategies.

scholarly journals The Status of Bile Acids and Farnesoid X Receptor in Brain and Liver of Rats with Thioacetamide-Induced Acute Liver Failure

2020 ◽  
Vol 21 (20) ◽  
pp. 7750
Author(s):  
Anna Maria Czarnecka ◽  
Krzysztof Milewski ◽  
Jan Albrecht ◽  
Magdalena Zielińska
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Bile Acids ◽  
Tissue Expression ◽  
Farnesoid X Receptor ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
The Status ◽  
The Brain

Acute liver failure (ALF) leads to neurological symptoms defined as hepatic encephalopathy (HE). Although accumulation of ammonia and neuroinflammation are generally accepted as main contributors to HE pathomechanism, a buildup of bile acids (BA) in the blood is a frequent component of liver injury in HE patients. Recent studies have identified the nuclear farnesoid X receptor (FXR) acting via small heterodimer partner (SHP) as a mediator of BA-induced effects in the brain of ALF animals. The present study investigated the status of the BA–FXR axis in the brain and the liver, including selective changes in pertinent genes in thioacetamide (TAA)-induced ALF in Sprague–Dawley rats. FXR was found in rat neurons, confirming earlier reports for mouse and human brain. BA accumulated in blood but not in the brain tissue. Expression of mRNAs coding for Fxr and Shp was reduced in the hippocampus and of Fxr mRNA also in the cerebellum. Changes in Fxr mRNA levels were not followed by changes in FXR protein. The results leave open the possibility that mobilization of the BA–FXR axis in the brain may not be necessarily pathognomonic to HE but may depend upon ALF-related confounding factors.

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