Abnormal brain oxygen homeostasis in an animal model of liver disease

Hadjihambi, Anna; Cudalbu, Cristina; Pierzchała, Katarzyna; Simicic, Dunja; Donnelly, Chris; Konstantinou, Christos; Davies, Nathan; Habtesion, Abeba; Gourine, Alexander V.; Jalan, Rajiv; Hosford, Patrick S.

doi:10.1016/j.jhepr.2022.100509

Cited by 16 publications

(12 citation statements)

References 56 publications

(74 reference statements)

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“…Very similar abnormalities have been described in some case reports in HE, but their pathogenesis was unclear (4). We hypothesize that cortical hypersignals on brain MRI in HE are related to decreased cortical oxygenation, mediated by hyperammonemia as described by Hadjihambi et al (1), potentially compromising brain energy metabolism as previously shown by us and others (5,6). We would like here to outline that brain lesions were reversible in our case with a strict control of ammonemia, together with control of the bleeding and symptomatic ICU management.…”

supporting

confidence: 65%

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Ammonia rises from the ashes!

Weiss

Thabut

2022

JHEP Reports

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supporting

confidence: 65%

“…We read with great interest the study by Hadjihambi et al. 1 showing that oxygen concentrations were reduced in the brains of rats with cirrhosis, which was probably mediated by hyperammonemia. The authors suggest that this brain hypoxia could participate in the pathogenesis of hepatic encephalopathy (HE), which is still a matter of debate.…”

mentioning

confidence: 98%

Ammonia rises from the ashes!

Weiss

Thabut

2022

JHEP Reports

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“…Notably, experimental studies indicate ammonia toxicity beyond its role in HE ( e.g. liver fibrogenesis and immune dysfunction 13 , 14 ). In a recent landmark study, Tranah et al.…”

Section: Introductionmentioning

confidence: 99%

Impact of ammonia levels on outcome in clinically stable outpatients with advanced chronic liver disease

Balcar¹,

Krawanja²,

Scheiner³

et al. 2023

JHEP Reports

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“…Iron-deficiency anemia is likely to occur in the presence of decreased TRF synthesis and Fe loss, which suggests that we need to pay attention to anemia indicators in CE and actively intervene when necessary. Ammonia, which is highly toxic to the central nervous system, is one of the end products of amino acid metabolism [38]. The liver is the only organ that can relieve ammonia toxicity.…”

mentioning

confidence: 99%

“…Ammonia, which is highly toxic to the central nervous system, is one of the end products of amino acid metabolism [38]. The liver is the only organ that can relieve ammonia toxicity.…”

mentioning

confidence: 99%

Effects of protoscoleces excretory-secretory products of Echinococcus granulosus on hepatocyte growth, function, and glucose metabolism

Luo

Lü³

et al. 2022

Preprint

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Cystic echinococcosis (CE) is one of the most widespread and harmful zoonotic parasitic diseases and it most commonly affects the liver. In this study, we characterized multiple changes in mouse hepatocytes following treatment with excretory-secretory (ES) products of Echinococcus granulosus protoscoleces by a factorial experiment. The cell counting kit-8 assay (CCK-8), the 5-ethynyl-2'-deoxyuridine (EdU) assay, and flow cytometry were used to detect the growth of hepatocytes. Inverted microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were used to observe the morphology and ultrastructure of hepatocytes. An automatic biochemical analyzer and an ELISA detection kit were used to determine six conventional hepatocyte enzymatic indices, the levels of five hepatocyte-synthesized substances, and the contents of glucose and lactate. Western blot analysis was conducted to analyze the protein expression of six rate-limiting enzymes in the glucose metabolism pathway in hepatocytes: glutamic-pyruvic transaminase (ALT), glutamic-oxalacetic transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), and leucine arylamidase (LAP). The results of the CCK-8 and EdU assays both showed that ES could inhibit the proliferation of hepatocytes, and flow cytometry indicated that ES could promote apoptosis of hepatocytes. After ES treatment, the ultrastructure of hepatocytes was disrupted to a certain extent. The changes in the cell membrane and microvilli were observed through SEM, and the changes in the nucleus, mitochondria, and rough endoplasmic reticulum were observed through TEM. After ES treatment, the enzymatic activities of the six hepatocyte enzymes were increased in addition to the Fe metabolism and the synthesis of albumin (ALB), uric acid (UA), and urea, whereas the synthesis of transferrin (TRF) was decreased. The expression levels of all six key enzymes in the glucose metabolism pathway in hepatocytes were decreased, and the biological effects were significantly inhibited. We analyzed the causes and possible complications caused by various changes and advocate corresponding measures. We also propose possible mechanisms by which protoscoleces cause hepatocyte necrosis, but the specific mechanism requires further study.

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Abnormal brain oxygen homeostasis in an animal model of liver disease

Cited by 16 publications

References 56 publications

Ammonia rises from the ashes!

Ammonia rises from the ashes!

Impact of ammonia levels on outcome in clinically stable outpatients with advanced chronic liver disease

Effects of protoscoleces excretory-secretory products of Echinococcus granulosus on hepatocyte growth, function, and glucose metabolism

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