title: Decrease of glutathione content in the prefrontal cortical mitochondria of rats with acute hepatic encephalopathy: prevention by histidine.
abstract: Mitochondrial glutathione (mGSH) is a critical factor in the cell defense against oxidative and nitrosative stress (ONS), and ONS is a key pathogenic event in hepatic encephalopathy (HE). Acute HE in the thioacetamide (TAA) model caused a 54 % decrease of mGSH content in the rat prefrontal cortex (pfc), but not in the striatum (str), nor did it affect the GSH content in the pfc or str homogenate. In the pfc, treatment with L- histidine (His), which is known to alleviate ONS-related symptoms in HE animals, attenuated the decrease of mGSH, and increased the GSH content in pfc and str homogenates and pfc microdialysates of control animals. His increased the expression of mRNA coding for the GSH synthesizing enzyme, glutamate cysteine ligase (GCL) and decreased that of the GSH-degrading enzyme γ-glutamyltranspeptidase (γGT). The results suggest that the decrease of mGSH may be an important contributing factor to mitochondrial dysfunction in HE, and delineate a new mechanistic aspect of the therapeutic potential of His in HE.
authors.affiliation: Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. joruszkiewicz@gmail.com
authors.forename: Joanna
authors.initials: J
authors.lastname: Ruszkiewicz
authors.forename: Inez
authors.initials: I
authors.lastname: Fręśko
authors.forename: Wojciech
authors.initials: W
authors.lastname: Hilgier
authors.forename: Jan
authors.initials: J
authors.lastname: Albrecht
mesh_terms: D000208:Acute Disease; D000818:Animals; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D005978:Glutathione / Q000032:analysis* / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000188:drug therapy / Q000378:metabolism*; D006639:Histidine / Q000627:therapeutic use*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006639:Histidine; C546365:GCLM protein, human; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione