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

Abstract

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.

An Altered Metabolism in Leukocytes Showing in vitro igG Memory From SARS-CoV-2-Infected Patients

“…The ratio of AdoMet to AdoHcy is frequently considered a metabolic gauge controlling in vivo methylation reactions, where a decrease in this ratio predicts reduced methylation capacity ( Czarnecka et al, 2020 ). These methylations are required for the 5′-cap formation of viral mRNAs.…”

Risk Factor Analysis of Hepatic Encephalopathy and the Establishment of Diagnostic Model

“…Homocysteine is a nonprotein-forming amino acid that can activate ionotropic glutamate N-methyl-aspartate (NMDA) receptors, thereby causing Ca 2+ to flow into neurons, which in turn activates several pathways, triggers oxidative stress, inflammation and apoptosis, and causes excitotoxicity [ 10 ]. Elevated levels of homocysteine in the plasma and brain develop hyperhomocysteinemia.…”

Rutin targets AKT to inhibit ferroptosis in ventilator‐induced lung injury

“…To verify whether rutin regulates ferroptosis in VILI mice, we performed a nontargeted metabolomic analysis of VILI model mice treated with rutin, and the results showed that rutin intervention increased the amount of glutathione disulfide (also known as oxidized glutathione) and decreased the amount of AdoHcy. AdoHcy is a competitive inhibitor of s‐adenosylmethionine (AdoMet)‐dependent trans‐methylation reactions, and the ratio of AdoMet/AdoHcy is predictive of the cellular methylation status (Czarnecka et al, 2020; Zanatta et al, 2017). AdoHcy can deplete cysteine, which is the metabolic precursor of glutathione, thus causing oxidative stress and reducing glutathione (Czarnecka et al, 2020; Zanatta et al, 2017).…”

“…AdoHcy is a competitive inhibitor of s‐adenosylmethionine (AdoMet)‐dependent trans‐methylation reactions, and the ratio of AdoMet/AdoHcy is predictive of the cellular methylation status (Czarnecka et al, 2020; Zanatta et al, 2017). AdoHcy can deplete cysteine, which is the metabolic precursor of glutathione, thus causing oxidative stress and reducing glutathione (Czarnecka et al, 2020; Zanatta et al, 2017). These results suggested that rutin may increase glutathione levels in the lung tissues of VILI mice.…”