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.

• Authors: Anna Maria Czarnecka, Wojciech Hilgier, Magdalena Zielińska
• Journal: Nutrients (Nutrients) Vol. 12 Issue 7 (Jul 17 2020) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 32709137 (Publication Type: Journal Article)

Chemical References

• Thioacetamide
• S-Adenosylmethionine
• S-Adenosylhomocysteine
• Mat1a protein, rat
• Methionine Adenosyltransferase
• Cystathionine beta-Synthase
• Glutathione

Topics

• Animals
• Brain (drug effects, metabolism)
• Cystathionine beta-Synthase (metabolism)
• Glutathione (metabolism)
• Hepatic Encephalopathy (etiology, metabolism)
• Liver (drug effects, metabolism)
• Liver Failure, Acute (chemically induced, metabolism)
• Male
• Methionine Adenosyltransferase (metabolism)
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley
• S-Adenosylhomocysteine (metabolism)
• S-Adenosylmethionine (metabolism)
• Thioacetamide (toxicity)