PMID- 24488205
OWN - NLM
STAT- MEDLINE
DCOM- 20151016
LR  - 20211021
IS  - 1573-7365 (Electronic)
IS  - 0885-7490 (Linking)
VI  - 29
IP  - 3
DP  - 2014 Sep
TI  - Glutathione metabolism enzymes in brain and liver of hyperphenylalaninemic rats 
      and the effect of lipoic acid treatment.
PG  - 609-15
LID - 10.1007/s11011-014-9491-x [doi]
AB  - Phenylketonuria (PKU) is a disorder caused by a deficiency in phenylalanine 
      hydroxylase activity, which converts phenylalanine (Phe) to tyrosine, leading to 
      hyperphenylalaninemia (HPA) with accumulation of Phe in tissues of patients. The 
      neuropathophysiology mechanism of disease remains unknown. However, recently the 
      involvement of oxidative stress with decreased glutathione levels in PKU has been 
      reported. Intracellular glutathione (GSH) levels may be maintained by the 
      antioxidant action of lipoic acid (LA). The aim of this study was to evaluate the 
      activity of the enzymes involved in the metabolism and function of GSH, such as 
      glutathione peroxidase (GSH-Px), glucose-6-phosphate dehydrogenase (G6PD), 
      glutathione reductase (GR), glutamate-cysteine ligase (GCL), 
      glutathione-S-transferase (GST) and GSH content in brain and liver of young rats 
      subjected to a chemically induced model of HPA and the effect of LA for a week. 
      In brain, the administration of Phe reduced the activity of the GSH-Px, GR and 
      G6PD and LA prevented these effects totally or partially. GCL activity was 
      increased by HPA and was not affect by LA antioxidant treatment. GST activity did 
      not differ between groups. GSH content was increased by LA and decreased by HPA 
      treatment in brain samples. Considering the liver, all parameters analyzed were 
      increased in studied HPA animals and LA was able to hinder some effects except 
      for the GCL, GST enzymes and GSH content. These results suggested that HPA model 
      alter the metabolism of GSH in rat brain and liver, which may have an important 
      role in the maintenance of GSH function in PKU although liver is not a directly 
      affected organ in this disease. So, an antioxidant therapy with LA may be useful 
      in the treatment of oxidative stress in HPA.
FAU - Moraes, Tarsila Barros
AU  - Moraes TB
AD  - Programa de Pos-Graduacao em Ciencias Biologicas: Bioquimica, Instituto de 
      Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Porto 
      Alegre, RS, Brazil, tarsilabio@yahoo.com.br.
FAU - Dalazen, Giovana Reche
AU  - Dalazen GR
FAU - Jacques, Carlos Eduardo
AU  - Jacques CE
FAU - de Freitas, Raylane Silva
AU  - de Freitas RS
FAU - Rosa, Andrea Pereira
AU  - Rosa AP
FAU - Dutra-Filho, Carlos Severo
AU  - Dutra-Filho CS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140202
PL  - United States
TA  - Metab Brain Dis
JT  - Metabolic brain disease
JID - 8610370
RN  - 73Y7P0K73Y (Thioctic Acid)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 1.8.1.7 (Glutathione Reductase)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/*enzymology
MH  - Glutathione/*metabolism
MH  - Glutathione Peroxidase/metabolism
MH  - Glutathione Reductase/metabolism
MH  - Glutathione Transferase/metabolism
MH  - Lipid Peroxidation/drug effects
MH  - Liver/drug effects/*enzymology
MH  - Oxidative Stress/drug effects
MH  - Phenylketonurias/*enzymology
MH  - Rats
MH  - Rats, Wistar
MH  - Thioctic Acid/*pharmacology
EDAT- 2014/02/04 06:00
MHDA- 2015/10/17 06:00
CRDT- 2014/02/04 06:00
PHST- 2013/06/28 00:00 [received]
PHST- 2014/01/16 00:00 [accepted]
PHST- 2014/02/04 06:00 [entrez]
PHST- 2014/02/04 06:00 [pubmed]
PHST- 2015/10/17 06:00 [medline]
AID - 10.1007/s11011-014-9491-x [doi]
PST - ppublish
SO  - Metab Brain Dis. 2014 Sep;29(3):609-15. doi: 10.1007/s11011-014-9491-x. Epub 2014 
      Feb 2.