Characterization of Oxidative Stress and Ammonia According to the Different Grades of Hepatic Encephalopathy

Abstract

Background: Hepatic encephalopathy (HE) in patients with chronic liver disease (CLD) is one of the main causes of reentry to the emergency department. Oxidative stress (OxS) regulated by ammonia leads to cerebral edema and astrocytes senescence in animal models, but seems to be different in humans. Objective: To analyze if OxS and ammonia in plasma are related to each other in the different grades of HE-CLD and to compare them with healthy volunteers (HV). Methods: In a cross-sectional study, we included 60 subjects in 2 groups: (a) 30 HV and (b) 30 HE patients. Plasma levels of oxidation lipids/proteins, ammonia, and West-Haven score were evaluated. Student t test, Spearman's correlation, and ANOVA with Dunn's post hoc test were performed. Results: Ammonia in HV and HE patients was 39-49 vs. 95-345 μmol/L, respectively (p < 0.0001). Malondialdehyde (MDA) in HV was 6.58 ± 3.11 compared to 16.69 ± 6.19 μmol/L in HE (p < 0.0001). Protein oxidation by osazone (carbonyls), formazan, and dityrosines was higher in HE than in HV (p < 0.0001). Ammonia level was directly associated to HE severity, but without correlation with lipid MDA or protein OxS formazan, carbonyls, and dityrosines. Lipid peroxidation showed higher levels at degree 2 and protein oxidation at degree 3 of HE. Conclusions:We confirm that OxS accompanies hyperammonemia in HE; however they contribute in different proportions to their natural progression. Early reduction of OxS in HE could contribute to minimize the neurotoxicity into CLD.

Polarity-regulated derivatization-assisted LC-MS method for amino-containing metabolites profiling in gastric cancer

“…The results showed that 3-DP-NHS derivatization has another advantage: it can be applied to the identification of low-molecular-weight metabolites. For example, metabolite with m/z 18.0344 was identified as ammonia, which has been proven to be associated with the progression of fibrosis in non-alcoholic fatty liver disease and hepatic encephalopathy severity [ 33 , 34 ]. Moreover, derivatization prevented interference from the low m/z region with small-molecule amino-containing compounds.…”

Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats

“…This happens both by an increase in extracellular glutamate levels and by direct ammonium activation of NMDA receptors. The NMDA receptor overstimulation is a crucial factor in the development of oxidative stress (Sathyasaikumar et al, 2007;Cittolin-Santos et al, 2017) due to the increase of calcium influx into the cell, which in turn increases ROS production (Hermenegildo et al, 2000;Montes-Cortes et al, 2019). The hepatectomy group presented elevated levels of ROS and decreased activity of SOD and GSH-Px (Figures 6B,C).…”

“…Previous studies demonstrated that cultured astrocytes treated with ammonia increased reactive oxygen species (ROS) levels, such as superoxide (Murthy et al, 2001), and the same effect was seen in a hyperammonemia rat model (Kosenko et al, 1997) and clinical studies (Montes-Cortes et al, 2019). Another study showed that ammonia increased mRNA levels of heme-oxygenase-1 (HO-1)-a typical marker of oxidative stress-in rats with HE (Warskulat et al, 2002).…”

Reduced Serum Cholinesterase Activity Distinguishes Hepatic Encephalopathy From 48 Types of Human Diseases

“…Increased blood ammonia levels have been considered as the main pathophysiological mechanism of HE [41,42] by causing swelling astrocytes, activation of microglia and neuroin ammation [43][44][45][46][47][48][49][50]. Microglia activation can promote the proliferation and release of pro-in ammatory cytokines [50], and the in ammation state can eventually lead to neuronal death [51].…”