On Aug 4, 8:13 pm, jay <jaym1...@hotmail.com> wrote: TCDD, a potent
form of dioxin, can cause cellular ROS<<
Looks like you may have to eat quite a bit though .
This seems to be an exact replica of increased iron in a mammal since
it causes such an increase in iron absorption.
It has been shown the same "accumulation of uroporphyrins" when the
iron levels in relation to vitamin C get .. skewed.
If there is more iron .. IE:"enhanced by iron" .. there is MORE ..
uroporphyrins JUST LIKE what happens in dioxin poisoning .. increased
iron at 45%.
So the Agent Orange 'problems' ARE iron related .. IE: porphyria
cutanea tarda.
Sooooo .. the 'reason' .. YOU .. 'see' the 'dioxin' .. connection is
BECAUSE you have run across an iron LOADING .. disease state /
condition / cause of all disease ..
Sooo .. you got the RESULT down.
IF everyone were poisoned by dioxin .. then you would have had the ..
exact .. pinpointed CAUSE .. but .. you fell short in THAT ..
particular department.
But you are right about the treatment ..
Iron reduction / targeting ..
"The mechanism may be oxidative in nature"
http://pubs.acs.org/cgi-bin/sample.c...tx700176r.html
ABSTRACT
The dysfunction of hepatic heme synthesis by 2,3,7,8-tetrachlordibenzo-
p-dioxin (TCDD) in mice, enhanced by iron, leads to accumulation of
uroporphyrins I and III (uroporphyria) and resembles the human
disorder porphyria cutanea tarda (PCT) precipitated by alcohol and
estrogenic drugs.
Although consequences of TCDD are considered entirely dependent on the
aryl hydrocarbon receptor (AHR), this is not proven for uroporphyria.
Administration of TCDD (75 µg/kg) caused uroporphyria in susceptible
C57BL/6J mice with high-affinity AHR after 5 weeks (>600-fold increase
in hepatic uroporphyrins).
Transcriptomics showed significant modified gene expressions for
intermediary, heme, and iron metabolism as well as for oxidative
stress and cell injury.
Resistant low-affinity AHR DBA/2 mice (no increase in porphyrins)
showed far fewer changes.
At this dose of TCDD, persistent up-regulation of some traditional AH
battery genes occurred in both strains.
Essentiality of AHR was demonstrated with C57BL/6 Ahr knockout mice.
Elevation of hepatic uroporphyrins was 964-fold in Ahr+/+ mice, lower
in Ahr+/- (60-fold), but undetectable with Ahr-/-.
Consistent with an oxidative mechanism, iron overload enhanced
porphyria as well as general liver injury in Ahr+/+ and Ahr+/- mice
but had no interactive effect in Ahr-/-.
In contrast, when iron-treated mice received, instead of TCDD, the
heme precursor 5-aminolevulinic acid (ALA), causing uroporphyia in Ahr
+/+ mice (242-fold rise in uroporphyrins), elevation of uroporphyrins
I and III (42-fold) also occurred in Ahr-/- mice and was seemingly
associated with AHR-independent expression of Cyp1a2. The findings
prove that AHR is a key factor in porphyria induced in mice by TCDD.
However, in other models of human PCT, participation of AHR may not be
an essential requirement.
-----------------
<<snip>>
ascorbate suppresses hepatic URO accumulation at low, but not high
hepatic iron levels
<<snip>>
Effect of iron and ascorbate on uroporphyria in ascorbate-requiring
mice as a model for porphyria cutanea tarda.
Gorman N, Zaharia A, Trask HS, Szakacs JG, Jacobs NJ, Jacobs JM,
Balestra D, Sinclair JF, Sinclair PR
Hepatology. 2006 Dec 22; 45(1): 187-194
Excess hepatic iron is known to enhance both porphyria cutanea tarda
(PCT) and experimental uroporphyria. Since previous studies have
suggested a role for ascorbate (AA) in suppressing uroporphyria in
AA-requiring rats (in the absence of excess iron), the present study
investigated whether AA could suppress uroporphyria produced by
excess
hepatic iron. Hepatic URO accumulation was produced in AA-requiring
Gulo(-/-) mice by treatment with 3,3',4,4',5-pentachlorbiphenyl, an
inducer of CYP1A2, and 5-aminolevulinic acid. Mice were administered
either sufficient AA (1000 ppm) in the drinking water to maintain
near
normal hepatic AA levels or a lower intake (75 ppm) that resulted in
70
% lower hepatic AA levels. The higher AA intake suppressed hepatic
URO
accumulation in the absence of administered iron, but not when iron
dextran (300-500 mg Fe/kg) was administered. This effect of iron was
not due to hepatic AA depletion since hepatic AA content was not
decreased. The effect of iron to prevent AA suppression of hepatic
URO
accumulation was not observed until a high hepatic iron threshold was
exceeded. At both low and high AA intakes, hepatic malondialdehyde
(MDA), an indicator of oxidative stress, was increased three-fold by
high doses of iron dextran. MDA was considerably increased even at
low
iron dextran doses, but without any increase in URO accumulation. The
level of hepatic CYP1A2 was unaffected by either AA intake.
Conclusion:
In this mouse model of PCT, AA suppresses hepatic URO accumulation at
low, but not high hepatic iron levels. These results may have
implications for the management of PCT. (HEPATOLOGY
2007;45:187-194.).
Abstract · PubMed FullText · SFX · GS Clip Export InterDB ·
Terms Related · Graph Tag · Scopus · Cites 10.1002/hep.21474
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
> > > via multiple pathways including one that uses iron.
>
> > You really are making it rather hard to understand what the article ..
> > says ... Iron chelator relieves .. sciatica ..
>
> Introduction of Iron Transport by a Potent Inducer of
> Aryl Hydrocarbon Hydroxylase,
> 2, 3, 7, 8--TetraChloroDibenzo-p-Dioxin (TCDD)
>
> A potent enzymatic inducer, TCDD, stimulates iron transport in the
> intestine of the rat. The stimulatory site in the intestine is more
> available to the inducer given orally than parenterally. Effects on
> intestinal absorptive mechanisms may be additional public health
> hazards of enzyme inducers such as TCDD. PMID: 453921
>
> TCDD, whose half life is 10 years in the humans, induces the above
> effect in nearly any cell it gets into, including nerves. The iron is
> used to construct one of many detox enzymes, one of which is shown athttp://www.p450.kvl.dk/gallery/Aligned_consensus_heme_full.jpg
> The raspberry-colored structures are made of iron. 
Acute Backache and Moderate Sciatica 
Linear Mode
