TY - JOUR
T1 - Oral administration of glutathione improves memory deficits following transient brain ischemia by reducing brain oxidative stress
AU - Yabuki, Y.
AU - Fukunaga, K.
N1 - Funding Information:
This work is supported in part by collaboration with the Healthcare Products Development Center, KYOWA HAKKO BIO CO., LTD. , and in part by grants-in-aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (Kakenhi 22390109 , 24102505 and 25293124 to K.F.) and the Smoking Research Foundation (to K.F.).
PY - 2013/10
Y1 - 2013/10
N2 - Oxidative stress aggravates brain injury following ischemia. The glutathione (GSH) system plays a pivotal role in combating oxidative stress in various cell types. To determine whether oral GSH administration elicits anti-oxidative effects, we assessed its potential neuroprotective effects in transient bilateral common carotid artery occlusion (BCCAO) mice. In naïve mice, acute oral administration of GSH significantly increased GSH levels by 1. h in the cortex and hippocampus. Eleven days after BCCAO, untreated mice showed significantly decreased GSH levels and an inverse elevation of glutathione-disulfide (GSSG) levels in both the cortex and hippocampus. Oral administration of GSH (100 and 500. mg/kg p.o.) for 10 consecutive days after ischemia restored reduced GSH levels and inhibited GSSG elevation. Notably, post-administration of GSH (100 and 500. mg/kg p.o.) significantly prevented neuronal cell death in the hippocampal CA1 region in BCCAO mice, an effect closely correlated with decreased levels of oxidative markers such as 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2-deoxyguanosine (8-OHdG) and nitrotyrosine in that region. Finally, GSH administration for 10. days improved memory deficits observed in BCCAO mice. Taken together, our findings indicate that the anti-oxidative effect of oral GSH administration ameliorates post-ischemia neuronal cell death and, in turn, may improve memory.
AB - Oxidative stress aggravates brain injury following ischemia. The glutathione (GSH) system plays a pivotal role in combating oxidative stress in various cell types. To determine whether oral GSH administration elicits anti-oxidative effects, we assessed its potential neuroprotective effects in transient bilateral common carotid artery occlusion (BCCAO) mice. In naïve mice, acute oral administration of GSH significantly increased GSH levels by 1. h in the cortex and hippocampus. Eleven days after BCCAO, untreated mice showed significantly decreased GSH levels and an inverse elevation of glutathione-disulfide (GSSG) levels in both the cortex and hippocampus. Oral administration of GSH (100 and 500. mg/kg p.o.) for 10 consecutive days after ischemia restored reduced GSH levels and inhibited GSSG elevation. Notably, post-administration of GSH (100 and 500. mg/kg p.o.) significantly prevented neuronal cell death in the hippocampal CA1 region in BCCAO mice, an effect closely correlated with decreased levels of oxidative markers such as 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2-deoxyguanosine (8-OHdG) and nitrotyrosine in that region. Finally, GSH administration for 10. days improved memory deficits observed in BCCAO mice. Taken together, our findings indicate that the anti-oxidative effect of oral GSH administration ameliorates post-ischemia neuronal cell death and, in turn, may improve memory.
KW - Bilateral common carotid arteries occlusion
KW - Ca/calmodulin-dependent protein kinase II
KW - Glutathione
KW - Neuroprotection
KW - Oxidative stress
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U2 - 10.1016/j.neuroscience.2013.07.017
DO - 10.1016/j.neuroscience.2013.07.017
M3 - Article
C2 - 23872392
AN - SCOPUS:84882626461
VL - 250
SP - 394
EP - 407
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
ER -