ironjustice

Role of glutathione in neuroprotective effects of mood stabilizing
drugs lithium and valproate.
Cui J, Shao L, Young LT, Wang JF
Neuroscience. 2006 Dec 18;

Mood stabilizing drugs lithium and valproate are the most commonly used
treatments for bipolar disorder. Previous studies in our laboratory
indicate that chronic treatment with lithium and valproate inhibits
oxidative damage in primary cultured rat cerebral cortical cells.
Glutathione, as the major antioxidant in the brain, plays a key role in
defending against oxidative damage. The purpose of this study was to
determine the role of glutathione in the neuroprotective effects of
lithium and valproate against oxidative damage. We found that chronic
treatment with lithium and valproate inhibited reactive oxygen
metabolite H(2)O(2)-induced cell death in primary cultured rat cerebral
cortical cells, while buthionine sulfoximine, an inhibitor of
glutathione rate-limiting synthesis enzyme glutamate-cysteine ligase,
reduced the neuroprotective effect of lithium and valproate against
H(2)O(2)-induced cell death. Further, we found that chronic treatment
with lithium and valproate increased glutathione levels in primary
cultured rat cerebral cortical cells and that the effects of lithium
and valproate on glutathione levels were dose-dependent in human
neuroblastoma SH-SY5Y cells. Chronic treatment with lithium and
valproate also increased the expression of glutamate-cysteine ligase in
both rat cerebral cortical cells and SH-SY5Y cells. In addition,
chronic treatment with other mood stabilizing drugs lamotrigine and
carbamazepine, but not antidepressants desipramine and fluoxetine,
increased both glutathione levels and the expression of
glutamate-cysteine ligase in SH-SY5Y cells. These results suggest that
glutathione plays an important role in the neuroprotective effects of
lithium and valproate, and that glutathione may be a common target for
mood stabilizing drugs.


Abstract · PubMed FullText · SFX · GS Clip Export InterDB ·
Terms Related · Graph Tag · Scopus · Cites
10.1016/j.neuroscience.2006.11.010
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<<snip>>
progressive iron ac***ulation leads to a progressive decrease in
glutathione content
<<snip>>

Free Radic Biol Med. 2004 Oct 1;37(7):953-60. Related Articles, Links


Progressive iron ac***ulation induces a biphasic change in the
glutathione content of neuroblastoma cells.


Nunez MT, Gallardo V, Munoz P, Tapia V, Esparza A, Salazar J, Speisky
H.


Department of Biology, Faculty of Sciences, Universidad de Chile,
Santiago, Chile.


Glutathione (GSH) constitutes the single most important antioxidant in
neurons, whereas iron causes oxidative stress that leads to cell damage

and death. Although GSH and iron produce opposite effects on redox cell

status, no mechanistic relationships between iron and GSH metabolism
are known. In this work, we evaluated in SH-SY5Y neuroblastoma cells
the effects of iron ac***ulation on intracellular GSH metabolism. After

2 d exposure to increasing concentrations of iron, cells underwent
concentration-dependent iron ac***ulation and a biphasic change in
intracellular GSH levels. Increasing iron from 1 to 5 microM resulted
in a marked increase in intracellular oxidative stress and increased
GSH levels. Increased GSH levels were due to increased synthesis.
Further increases in iron concentration led to significant reduction in

both reduced (GSH) and total (GSH + (2 x GSSG)) glutathione. Cell
exposure to high iron concentrations (20-80 microM) was associated with

a marked decrease in the GSH/GSSG molar ratio and the GSH half-cell
reduction potential. Moreover, increasing iron from 40 to 80 microM
resulted in loss of cell viability. Iron loading did not change GSH
reductase activity but induced significant increases in GSH peroxidase
and GSH transferase activities. The changes in GSH homeostasis reported

here recapitulate several of those observed in Parkinson's disease
substantia nigra. These results support a model by which progressive
iron ac***ulation leads to a progressive decrease in GSH content and
cell reduction potential, which finally results in impaired cell
integrity.


PMID: 15336311 [PubMed - in process]


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Glutathione raised by phlebotomy / bloodletting ..


Comp Biochem Physiol B. 1983;75(1):5-8. Related Articles, Links

Effect of experimental anaemia on red cell GSH and enzyme activities in

guinea-pig and rabbit.

Suzuki M, Kataoka T.


1. The effect of experimental anaemia on red cell GSH and enzyme
activities of GSH-Px, GSSG-R and G6PD was investigated in guinea-pig
and rabbit. 2. The anaemia was induced by injection of PHH in
guinea-pig and rabbit and also by bleeding in guinea-pig. 3. Red cell
GSH increased from 115.5 to 141.8 mg/dl RBC in the guinea-pig and from
108.5 to 133.5 mg/dl RBC in the rabbit during anaemia. 4. There were
significant rises in the level of all the three enzymes activities in
both the species of animals. However, the changes in rabbit were more
pronounced than in the guinea-pig.


PMID: 6851486 [PubMed - indexed for MEDLINE]


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1: Aust J Biol Sci. 1975 Jun;28(3):233-8. Related Articles, Links


The effect of experimental anaemia on the levels of glutathione and
glycolytic enzymes of the erythrocytes of normal and
glutathione-deficient Merino sheep.


Agar NS, Roberts J, Mulley A, Board PG, Harley JD.


The effects of experimental anaemia on the levels of reduced
glutathione (GSH) and the activity of glycolytic enzymes in the
erythrocytes of normal and GSH-deficient Merino sheep were
investigated. There was a rise in red cell GSH levels in both groups of

sheep; the magnitude of this response was, however, quite different.
When expressed as a percentage of the initial value, the rise in GSH
level was 18% in normal and 263% in GSH-deficient animals. There was
also an increase in the activities of various enzymes following
phlebotomy but this increase was similar in the two groups of sheep.


PMID: 126681 [PubMed - indexed for MEDLINE]


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