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Home > Archive > Pathology > September 2005 > Iron and arachidonic acid synergistically produce cell toxicity
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Iron and arachidonic acid synergistically produce cell toxicity
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| ironjustice@aol.com 2005-08-16, 8:57 am |
| Would / could this relate to anaphylactic shock at all .. ?
In that transferrin saturation was shown to be related to anaphylactic
shock.. in another study .. http://tinyurl.com/8mkr5
Toxicology and Applied Pharmacology
Article in Press, Corrected Proof - Note to users
doi:10.1016/j.taap.2005.01.057
Copyright =A9 2005 Elsevier Inc. All rights reserved.
Oxidative stress mediated toxicity exerted by ethanol-inducible CYP2E1
Defeng Wu and Arthur I. Cederbaum,
Department of Pharmacology and Biological Chemistry, Box 1603, Mount
Sinai School of Medicine, One Gustave L. Levy Place, New York, NY
10029, USA
Received 15 July 2004; revised 10 January 2005; accepted 10 January
2005. Available online 12 July 2005.
Abstract
Induction of CYP2E1 by ethanol is one of the central pathways by which
ethanol generates a state of oxidative stress in hepatocytes. To study
the biochemical and toxicological actions of CYP2E1, our laboratory
established HepG2 cell lines which constitutively overexpress CYP2E1
and characterized these cells with respect to ethanol toxicity.
Addition of ethanol or an unsaturated fatty acid such as arachidonic
acid or iron was toxic to the CYP2E1-expressing cells but not control
cells. This toxicity was associated with elevated lipid peroxidation
and could be prevented by antioxidants and inhibitors of CYP2E1.
Apoptosis occurred in the CYP2E1-expressing cells exposed to ethanol,
arachidonic acid, or iron. Removal of GSH caused a loss of viability in
the CYP2E1-expressing cells even in the absence of added toxin or
pro-oxidant. This was associated with mitochondrial damage and
decreased mitochondrial membrane potential. Low concentrations of iron
and arachidonic acid synergistically interacted with CYP2E1 to produce
cell toxicity, suggesting these nutrients may act as priming or
sensitizing agents to alcohol-induced liver injury. Surprisingly,
CYP2E1-expressing cells had elevated GSH levels, due to transcriptional
activation of glutamate cysteine ligase. Similarly, levels of catalase,
alpha-, and microsomal glutathione transferase were also increased,
suggesting that upregulation of these antioxidant genes may reflect an
adaptive mechanism to remove CYP2E1-derived oxidants. Using
co-cultures, interaction between CYP2E1-derived diffusible mediators to
activate collagen production in hepatic stellate cells was found. While
it is likely that several mechanisms contribute to alcohol-induced
liver injury, the linkage between CYP2E1-dependent oxidative stress,
mitochondrial injury, stellate cell activation, and GSH homeostasis may
contribute to the toxic action of ethanol on the liver. HepG2 cell
lines overexpressing CYP2E1 may be a valuable model to characterize the
biochemical and toxicological properties of CYP2E1.
Keywords: CYP2E1; Oxidative stress; Cytotoxicity; Antioxidant genes
Abbreviations: CYP2E1, cytochrome P4502E1; GSH, glutathione; MMP,
mitochondrial membrane potential; PUFA, polyunsaturated fatty acid;
CCl4, carbon tetrachloride; E9 cells, HepG2 cells established by
retroviral infection methods which express CYP2E1; E47 cells, HepG2
cells established by plasmid transfection methods which express CYP2E1;
MV5 or C34 cells, control HepG2 cells which do not express CYP2E1; NTA,
nitrilotriacetate; BSO, buthionine-l-sulfoximine; HSC, hepatic stellate
cells; ROS, reactive oxygen species; AA, arachidonic acid; GCL,
glutamate-cysteine ligase
Corresponding author. Fax: +1 212 996 7214.
Toxicology and Applied Pharmacology
Article in Press, Corrected Proof
Copyright =A9 2005 Elsevier B.V. All rights reserved. ScienceDirect=AE is
a registered trademark of Elsevier B.V.
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://jesuswasavegetarian.7h.com
Man Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore
DEAD PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking
---------------------------------------------------------------------------=
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| outsor@citynet.net 2005-08-16, 5:56 pm |
| "Would / could this relate to anaphylactic shock at all .. ? In that
transferrin saturation was shown to be related to anaphylactic shock."
No, a careful reading of the article says "saturation" was not an issue,
alcohol saturation was:
"Low concentrations of iron
and arachidonic acid synergistically interacted with CYP2E1 to produce
cell toxicity, suggesting these nutrients may act as priming or
sensitizing agents to alcohol-induced liver injury."
| |
| Mortimer Schnerd, RN 2005-08-16, 5:56 pm |
| outsor@citynet.net wrote:
> "Would / could this relate to anaphylactic shock at all .. ? In that
> transferrin saturation was shown to be related to anaphylactic shock."
>
> No, a careful reading of the article says "saturation" was not an issue,
> alcohol saturation was:
>
> "Low concentrations of iron
> and arachidonic acid synergistically interacted with CYP2E1 to produce
> cell toxicity, suggesting these nutrients may act as priming or
> sensitizing agents to alcohol-induced liver injury."
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| montygram 2005-08-16, 10:55 pm |
| Just go to pubmed.com and search for arachidonic. You'll see hundreds
of studies that demonstrate how dangerous arachidonic acid is. You can
also search for its metaoblites, especially PGE2 and LTB4.
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| ironjustice@aol.com 2005-08-16, 10:55 pm |
| You misunderstood the .. saturation .. bit ..
The saturation comes into it .. in the iron / transferrin .. end .. as
evidenced below ..
So how does the transferrin / iron 'saturation' .. 'come into it' .. ?
Is / does it say the more iron the easier the reaction .. ? or .. less
... ?
Ann Inst Pasteur Immunol. 1987 Mar-Apr;138(2):213-21. Related Articles,
Links
Biological effect of transferrin on mast cell mediator release during
the passive cutaneous anaphylaxis reaction: a possible inhibition
mechanism involving iron.
Mecheri S, Peltre G, Lapeyre J, David B.
A purification procedure for passive cutaneous anaphylaxis inhibitory
factor from BALB/c mouse serum has been previously described. In the
present work, this inhibitory activity was found to be related to
transferrin. No activity was obtained using iron-unsaturated
transferrin, whereas iron-saturated transferrin appeared to be potent.
The in vivo inhibition of IgE-dependent mediator release from rat mast
cells was also obtained using free iron. This effect was observed when
iron was injected prior to or simultaneously with mouse IgE in rat
skin. Iron and iron-saturated transferrin could play a role in the
mechanism of desensitization by modulating the responsiveness of mast
cells.
PMID: 2440461 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://jesuswasavegetarian.7h.com
Man Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore
DEAD PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking
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| outsor@citynet.net 2005-08-18, 11:53 am |
| "You misunderstood the .. saturation .. bit .."
No, it was misapplied, which is worse then not understanding, it is
steering data to fit a favorite notion. Saturation was low, abuse of
alcohol was the causal factor here.
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| ironjustice@aol.com 2005-08-18, 11:54 am |
| Actually .. the fact you didn't even .. KNOW ..what I was talking about
... IE: which 'saturation' .. I was talking about .. pretty much gives
one the idea .. you are attempting to .. act .. like you DO .. know ..
at least a little .. bit ..
But .. alas ..
You are just another fkg .. poser ..
Heh .. heh ..
Iron IS .. involved .. transferrin SATURATION .. is .. involved .. and
the fact you say it ISN'T involved when the article specifically SHOWS
it IS .. involved .. just the full MEANING of .. involvement is ..
unknown ..
So the fact YOU saying it is .. NOT .. involved .. makes your
stupidity .. or .. outright .. deceit .. troubling ..
Because .. stupidity .. is useless and deceit .. deserves a fkg ..
beating ..
So either way .. read my lips ..
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://jesuswasavegetarian.7h.com
Man Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore
DEAD PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking
Dig ..
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| Mortimer Schnerd, RN 2005-08-18, 11:54 am |
| outsor@citynet.net wrote:
> "You misunderstood the .. saturation .. bit .."
>
> No, it was misapplied, which is worse then not understanding, it is
> steering data to fit a favorite notion. Saturation was low, abuse of
> alcohol was the causal factor here.
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| outsor@citynet.net 2005-08-18, 5:55 pm |
| The activity of iron in the article was a tertiary effect of a liver
disorder resulting from alcohol abuse, it was the hair at the end of the
tail of the dog.
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| dcholiman@ev1.net 2005-08-21, 8:53 am |
| ~~~~~~~~~~~~~~~~~~~~~~~
You are taxing my medical knowledge here.
I thought iron supplements were bad for heart patients.
Is the "HG" in the serology the test for iron in
the blood ? If so, what are the normal limits ?
David H
~~~~~~~~~~~~~~~~
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| ironjustice@aol.com 2005-08-22, 11:55 am |
| >>
You are taxing my medical knowledge here.
I thought iron supplements were bad for heart patients.
Is the "HG" in the serology the test for iron in
the blood ? If so, what are the normal limits ?
David H
~~~~~~~~~~~~~~~~
<<
The guy is nuts ..
Figures giving an oxidative stress enhancer to a person IN a 'state' ..
OF .. oxidative stress is a .. good .. thing ..
Doesn't have any idea as to how .. odds .. equate .. just uses what
little ability he does .. have .. to ATTEMPT .. to .. deceive ..
You .. being a man .. have zero chances of being iron .. deficient ..
HE .. would have you believe you .. do ..
Which leads us to your .. conclusion .. ?
Taking iron ..
As I said .. the guy doesn't REALLY ... care .. WHETHER .. the
'reference' he made would lead you to take a substance which ODDS ON
... is .. bad .. therefore INCREASING the chances OF .. your ..
'hastening of death' ..
Watch .. yourself ..
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://jesuswasavegetarian.7h.com
Man Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore
DEAD PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking
| |
| Manky Badger 2005-08-22, 5:52 pm |
|
<ironjustice@aol.com> wrote in message
news:1124726884.469914.136150@g44g2000cwa.googlegroups.com...
> You .. being a man .. have zero chances of being iron .. deficient ..
OK Tom, straight question.
Why does being a man give you zero chance of being iron deficient ?
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| ironjustice@aol.com 2005-08-23, 8:54 am |
| I'll answer the question because .. I'm pretty sure .. you DON'T ..
actually .. KNOW ..
Heh .. heh ..
The human controls the iron it has in the body BY absorption. It
upregulates or downregulates the PERCENTAGE of iron it absorbs just to
keep the STORES .. 'topped up' ..
He has been eating meat since he was one year old.
So every day he ate meat he has absorbed at a very high rate the iron
from meat EVEN THOUGH his body is attempting NOT to absorb the iron
from his food ..
So being he is a man .. and has NO WAY to eliminate / excrete iron once
it gets INTO the body .. he is iron overloaded ..
No two ways about it .
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://jesuswasavegetarian.7h.com
Man Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore
DEAD PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking
| |
| outsor@citynet.net 2005-08-23, 5:55 pm |
| "So being he is a man .. and has NO WAY to eliminate / excrete iron once
it gets INTO the body .. he is iron overloaded .."
No, the body does have ways to get rid of iron, I'm surprised you didn't
know this. "Overloaded" is relative to some goal and it depends on how
much is consumed each day. If it is too high the ways of elimination
don't match the intake, that is a more valid statement of the question.
By medical definition only a few percent of the population is "overloaded"
at an increased risk level.
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| Manky Badger 2005-08-23, 5:55 pm |
|
<ironjustice@aol.com> wrote in message
news:1124796780.577536.9560@g14g2000cwa.googlegroups.com...
> I'll answer the question because .. I'm pretty sure .. you DON'T ..
> actually .. KNOW ..
>
> Heh .. heh ..
>
> The human controls the iron it has in the body BY absorption. It
> upregulates or downregulates the PERCENTAGE of iron it absorbs just to
> keep the STORES .. 'topped up' ..
>
> He has been eating meat since he was one year old.
> So every day he ate meat he has absorbed at a very high rate the iron
> from meat EVEN THOUGH his body is attempting NOT to absorb the iron
> from his food ..
>
> So being he is a man .. and has NO WAY to eliminate / excrete iron once
> it gets INTO the body .. he is iron overloaded ..
>
> No two ways about it .
OK - how about the case of the adult male with gastro-intestinal bleeding
who is losing blood through (for example) a bleeding ulcer.
Surely that person may well be in a position where their iron loss (through
bleeding) outweighs their dietry iron intake ?
..
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| Manky Badger 2005-09-24, 2:00 pm |
|
"Manky Badger" <spam@puritanDOTfreeserve.FULLSTOPcoSPOTuk> wrote in message
news:deg6v6$ie9$1@newsg4.svr.pol.co.uk...
>
> <ironjustice@aol.com> wrote in message
> news:1124796780.577536.9560@g14g2000cwa.googlegroups.com...
>
> OK - how about the case of the adult male with gastro-intestinal bleeding
> who is losing blood through (for example) a bleeding ulcer.
> Surely that person may well be in a position where their iron loss
> (through bleeding) outweighs their dietry iron intake ?
????? !
| |
| Manky Badger 2005-09-24, 2:08 pm |
|
"Manky Badger" <spam@puritanDOTfreeserve.FULLSTOPcoSPOTuk> wrote in message
news:deg6v6$ie9$1@newsg4.svr.pol.co.uk...
>
> <ironjustice@aol.com> wrote in message
> news:1124796780.577536.9560@g14g2000cwa.googlegroups.com...
>
> OK - how about the case of the adult male with gastro-intestinal bleeding
> who is losing blood through (for example) a bleeding ulcer.
> Surely that person may well be in a position where their iron loss
> (through bleeding) outweighs their dietry iron intake ?
????? !
| |
| Manky Badger 2005-09-24, 2:11 pm |
|
"Manky Badger" <spam@puritanDOTfreeserve.FULLSTOPcoSPOTuk> wrote in message
news:deg6v6$ie9$1@newsg4.svr.pol.co.uk...
>
> <ironjustice@aol.com> wrote in message
> news:1124796780.577536.9560@g14g2000cwa.googlegroups.com...
>
> OK - how about the case of the adult male with gastro-intestinal bleeding
> who is losing blood through (for example) a bleeding ulcer.
> Surely that person may well be in a position where their iron loss
> (through bleeding) outweighs their dietry iron intake ?
????? !
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