title: Changes of the thioredoxin system, glutathione peroxidase activity and total antioxidant capacity in rat brain cortex during acute liver failure: modulation by L-histidine.
abstract: Glutathione and thioredoxin are complementary antioxidants in the protection of mammalian tissues against oxidative-nitrosative stress (ONS), and ONS is a principal cause of symptoms of hepatic encephalopathy (HE) associated with acute liver failure (ALF). We compared the activities of the thioredoxin system components: thioredoxin (Trx), thioredoxin reductase (TrxR) and the expression of the thioredoxin-interacting protein, and of the key glutathione metabolizing enzyme, glutathione peroxidase (GPx) in the cerebral cortex of rats with ALF induced by thioacetamide (TAA). ALF increased the Trx and TrxR activity without affecting Trip protein expression, but decreased GPx activity in the brains of TAA-treated rats. The total antioxidant capacity (TAC) of the brain was increased by ALF suggesting that upregulation of the thioredoxin may act towards compensating impaired protection by the glutathione system. Intraperitoneal administration of L-histidine (His), an amino acid that was earlier reported to prevent acute liver failure-induced mitochondrial impairment and brain edema, abrogated most of the acute liver failure-induced changes of both antioxidant systems, and significantly increased TAC of both the control and ALF-affected brain. These observations provide further support for the concept of that His has a potential to serve as a therapeutic antioxidant in HE. Most of the enzyme activity changes evoked by His or ALF were not well correlated with alterations in their expression at the mRNA level, suggesting complex translational or posttranslational mechanisms of their modulation, which deserve further investigations.
authors.affiliation: Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106, Warsaw, Poland, joruszkiewicz@gmail.com.
authors.forename: Joanna
authors.initials: J
authors.lastname: Ruszkiewicz
authors.forename: Jan
authors.initials: J
authors.lastname: Albrecht
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006639:Histidine / Q000494:pharmacology*; D017114:Liver Failure, Acute / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013879:Thioredoxins / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D006639:Histidine; D013879:Thioredoxins; D005979:Glutathione Peroxidase