Ironjustic
Tue, Sep-25-07, 17:16
It seems the iron overload in thalassemia is being targeted
with .. natural iron chelators like milk thistle .. and
getting much better results by adding a little .. lecithin /
phosphatidylcholine.
<<snip>> Thalassemia major is characterized by anemia, iron
overload, and oxidant damage to major organs, especially the
cardiovascular system.
Although silymarin is a complex of 7 flavonolignans and
polyphenols, silibinin is usually regarded as the most active
component.
GSH restoration and improvement of PBMC growth by silymarin is
a possible explanation for its recently reported antioxidant
and immunostimulatory activities.
Silybin administration significantly reduced bothfunctional
anomalies and the fibrotic process by chelating
desferrioxamine chelatable iron. <<snip>>
Pediatr Cardiol. 2007 Sep 22; [Epub ahead of print]
Endothelial Dysfunction and Oxidant Status in Pediatric
Patients with Hemoglobin E-beta Thalassemia. Kukongviriyapan
V, Somparn N, Senggunprai L, Prawan A, Kukongviriyapan U,
Jetsrisuparb A. Department of Pharmacology, Faculty of
Medicine, Khon Kaen University, Khon Kaen, Thailand, 40002,
veerapol@kku.ac.th.
Thalassemia major is characterized by anemia, iron overload,
and oxidant damage to major organs, especially the
cardiovascular system. Oxidative stress is ultimately involved
in endothelial dysfunction, a condition which is evident in
adults suffering from various cardiovascular diseases
including thalassemia. We investigated endothelial function in
pediatric patients with hemoglobin E-beta thalassemia
(HbE-beta thalassemia), who have been exposed to excessive
iron and oxidative stress for much shorter period than adults
with thalassemia. We recruited 22 blood transfusion-dependent
HbE-beta thalassemia patients aged 11.8 +/- 2.9 years and 20
healthy controls aged 12.1 +/- 1.7 years. Oxidant status was
determined, and endothelial function was assessed by a forearm
blood flow technique. Oxidative stress was increased in the
thalassemic patients, as blood glutathione (GSH) and ratios of
reduced GSH to GSH disulfide were markedly reduced, and
superoxide anion released from blood cells was highly
elevated. Oxidative stress response, assessed by gamma-
glutamylcysteine ligase activity, was increased approximately
twofold in thalassemia patients. Basal forearm blood flow was
significantly increased in patients compared with controls
(7.3 +/- 1.8 vs 6.0 +/- 1=2E8 ml/100 ml tissue/min,
respectively), whereas forearm vasodilatory response to
reactive hyperemia was depressed by 50% in patients compared
with controls. Endothelial function is impaired in young
thalassemia patients, and impaired endothelial function is
associated with oxidant stress.
PMID: 17891513 [PubMed - as supplied by publisher]
-----------------------------------------------------------
Int Immunopharmacol. 2006 Aug;6(8):1305-10. Epub 2006 May 2.
Links Effects of silymarin on the proliferation and
glutathione levels of peripheral blood mononuclear cells from
beta-thalassemia major patients. Alidoost F, Gharagozloo M,
Bagherpour B, Jafarian A, Sajjadi SE, Hourfar H, Moayedi B.
Department of Immunology, School of Medicine, Hezar Jerib
Avenue, Isfahan University of Medical Sciences, Isfahan, Iran.
Iron toxicity in beta-thalassemia major is the main cause of
oxidative stress and cell mediated immune deficiencies.
Despite indicative signs of severe oxidative deficiencies
associated with beta-thalassemia major, such as decreased
level of plasma antioxidants and depletion of erythrocyte
glutathione, little is known about intracellular redox status
of immune cells. Since glutathione is a primary intracellular
antioxidant and plays an essential role in several functions
in T cells, in this study intracellular glutathione (GSH)
levels as well as proliferation of PHA-activated peripheral
blood mononuclear cells (PBMC) were investigated in 28
beta-thalassemia major patients and 28 healthy age-matched
individuals. Considering the potential benefits of flavonoids
in the therapy of oxidative stress, the effects of silymarin
on the GSH levels and proliferation of PBMC from normal and
thalassemia individuals were further examined. Quantitative
determination of intracellular GSH and proliferative response
of PBMC to PHA were performed before and after 72 h incubation
of PBMC with various concentrations of silymarin (0, 5, 10, or
20 mug/ml). Results demonstrated a significant reduction of
GSH and proliferation in beta- thalassemia major cells;
however treatment with silymarin led to restoration of both
GSH levels and PBMC proliferation in thalassemia patients.
Considerably low levels of GSH and depressed proliferative
response of PBMC in beta-thalassemia major may be responsible
for the cell mediated immune abnormalities in iron overload
conditions. Moreover, the GSH restoration and improvement of
PBMC growth by silymarin is a possible explanation for its
recently reported antioxidant and immunostimulatory
activities. These data suggest the benefit of using flavonoids
to normalize immune dysfunction in beta- thalassemia major.
The immunomodulatory effects of silymarin in beta- thalassemia
major are currently under further investigation in a double
blind clinical trial.
PMID: 16782543 [PubMed - indexed for MEDLINE] ----------------
------------------------------------------------------------=
---
J Vet Pharmacol Ther. 2007 Apr;30(2):132-8. Links
Bioavailability of a silybin-phosphatidylcholine complex in
dogs. Filburn CR, Kettenacker R, Griffin DW. Veterinary
Science Division, Nutramax Laboratories, Inc., Edgewood, MD
21040, USA.
Liver dysfunction often is associated with an imbalance in the
production and removal of free radicals derived from oxygen
and nitrogen and has been managed clinically with antioxidant
supplements, including silymarin extract derived from milk
thistle. The potential for enhanced bioavailability of a
phytosome complex containing phosphatidylcholine and silybin,
the primary active flavonolignan in silymarin extract, was
tested in dogs. A group of eight beagles (four males, four
females) were dosed orally with a silybin- phosphatidylcholine
complex (SPC) and a commercially available standardized
silymarin extract containing equivalent levels of silybin.
Dosing with the SPC resulted in Cmax, Tmax, and AUC0-24 h
values (mean+/-SD) for total silybin of 1310+/-880 ng/mL,
2.87+/-2.23 h, and 11,200+/-6520 ng.h/mL, respectively;
corresponding values for a standardized silymarin extract were
472+/-383 ng/mL, 4.75+/-2.82 h, and 3720+/-4970 ng.h/mL. A
second, separate group of beagles were also dosed with the
extract alone, yielding values of 449+/-402 ng/mL,
6=2E87+/-7.43 h, and 2520+/-2976 ng.h/mL. These data show that
a phytosome complex of phosphatidylcholine and silybin
markedly enhances bioavailability in dogs.
PMID: 17348898 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
---------------
<<snip>> Silybin administration significantly reduced
bothfunctional anomalies and the fibrotic process by chelating
desferrioxamine chelatable iron. <<snip>>
Alberto Masini1 , Daniela Ceccarelli2, Fabiola Giovannini2,
Giuliana Montosi2, Cinzia Garuti2 and Antonello Pietrangelo2
(1) Sezione di Patologia Generale, Dipartimento di Scienze
Biomediche, Universita di Modena, Modena, Italy
(2) Dipartimento di Medicina Interna, Universit=E0 di Modena,
Modena, Italy
Abstract Hepatic iron toxicity because of iron overload seems
to be mediated by lipid peroxidation ofbiological membranes
and the associated organelle dysfunctions. However, the
basicmechanisms underlying this process in vivo are still
little understood. Gerbils were dosed with weeklyinjections
of iron-dextran alone or in combination with sylibin, a
well-known antioxidant,by gavage for 8 weeks. A strict
correlation was found between lipid peroxidation and the
levelof desferrioxamine chelatable iron pool. A consequent
derangement in the mitochondrialenergy-transducing
capability, resulting from a reduction in the respiratory
chain enzymeactivities, occurred. These irreversible
oxidative anomalies brought about a dramatic drop intissue
ATP level. The mitochondrial oxidative derangement was
associated with thedevelopment of fibrosis in the hepatic
tissue. Silybin administration significantly reduced
bothfunctional anomalies and the fibrotic process by
chelating desferrioxamine chelatable iron. Iron - oxidant
stress - liver mitochondria (gerbil)
--------------------------------------------------------------
--------------=
-----
Alberto Masini Email: masini@unimo.it
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
with .. natural iron chelators like milk thistle .. and
getting much better results by adding a little .. lecithin /
phosphatidylcholine.
<<snip>> Thalassemia major is characterized by anemia, iron
overload, and oxidant damage to major organs, especially the
cardiovascular system.
Although silymarin is a complex of 7 flavonolignans and
polyphenols, silibinin is usually regarded as the most active
component.
GSH restoration and improvement of PBMC growth by silymarin is
a possible explanation for its recently reported antioxidant
and immunostimulatory activities.
Silybin administration significantly reduced bothfunctional
anomalies and the fibrotic process by chelating
desferrioxamine chelatable iron. <<snip>>
Pediatr Cardiol. 2007 Sep 22; [Epub ahead of print]
Endothelial Dysfunction and Oxidant Status in Pediatric
Patients with Hemoglobin E-beta Thalassemia. Kukongviriyapan
V, Somparn N, Senggunprai L, Prawan A, Kukongviriyapan U,
Jetsrisuparb A. Department of Pharmacology, Faculty of
Medicine, Khon Kaen University, Khon Kaen, Thailand, 40002,
veerapol@kku.ac.th.
Thalassemia major is characterized by anemia, iron overload,
and oxidant damage to major organs, especially the
cardiovascular system. Oxidative stress is ultimately involved
in endothelial dysfunction, a condition which is evident in
adults suffering from various cardiovascular diseases
including thalassemia. We investigated endothelial function in
pediatric patients with hemoglobin E-beta thalassemia
(HbE-beta thalassemia), who have been exposed to excessive
iron and oxidative stress for much shorter period than adults
with thalassemia. We recruited 22 blood transfusion-dependent
HbE-beta thalassemia patients aged 11.8 +/- 2.9 years and 20
healthy controls aged 12.1 +/- 1.7 years. Oxidant status was
determined, and endothelial function was assessed by a forearm
blood flow technique. Oxidative stress was increased in the
thalassemic patients, as blood glutathione (GSH) and ratios of
reduced GSH to GSH disulfide were markedly reduced, and
superoxide anion released from blood cells was highly
elevated. Oxidative stress response, assessed by gamma-
glutamylcysteine ligase activity, was increased approximately
twofold in thalassemia patients. Basal forearm blood flow was
significantly increased in patients compared with controls
(7.3 +/- 1.8 vs 6.0 +/- 1=2E8 ml/100 ml tissue/min,
respectively), whereas forearm vasodilatory response to
reactive hyperemia was depressed by 50% in patients compared
with controls. Endothelial function is impaired in young
thalassemia patients, and impaired endothelial function is
associated with oxidant stress.
PMID: 17891513 [PubMed - as supplied by publisher]
-----------------------------------------------------------
Int Immunopharmacol. 2006 Aug;6(8):1305-10. Epub 2006 May 2.
Links Effects of silymarin on the proliferation and
glutathione levels of peripheral blood mononuclear cells from
beta-thalassemia major patients. Alidoost F, Gharagozloo M,
Bagherpour B, Jafarian A, Sajjadi SE, Hourfar H, Moayedi B.
Department of Immunology, School of Medicine, Hezar Jerib
Avenue, Isfahan University of Medical Sciences, Isfahan, Iran.
Iron toxicity in beta-thalassemia major is the main cause of
oxidative stress and cell mediated immune deficiencies.
Despite indicative signs of severe oxidative deficiencies
associated with beta-thalassemia major, such as decreased
level of plasma antioxidants and depletion of erythrocyte
glutathione, little is known about intracellular redox status
of immune cells. Since glutathione is a primary intracellular
antioxidant and plays an essential role in several functions
in T cells, in this study intracellular glutathione (GSH)
levels as well as proliferation of PHA-activated peripheral
blood mononuclear cells (PBMC) were investigated in 28
beta-thalassemia major patients and 28 healthy age-matched
individuals. Considering the potential benefits of flavonoids
in the therapy of oxidative stress, the effects of silymarin
on the GSH levels and proliferation of PBMC from normal and
thalassemia individuals were further examined. Quantitative
determination of intracellular GSH and proliferative response
of PBMC to PHA were performed before and after 72 h incubation
of PBMC with various concentrations of silymarin (0, 5, 10, or
20 mug/ml). Results demonstrated a significant reduction of
GSH and proliferation in beta- thalassemia major cells;
however treatment with silymarin led to restoration of both
GSH levels and PBMC proliferation in thalassemia patients.
Considerably low levels of GSH and depressed proliferative
response of PBMC in beta-thalassemia major may be responsible
for the cell mediated immune abnormalities in iron overload
conditions. Moreover, the GSH restoration and improvement of
PBMC growth by silymarin is a possible explanation for its
recently reported antioxidant and immunostimulatory
activities. These data suggest the benefit of using flavonoids
to normalize immune dysfunction in beta- thalassemia major.
The immunomodulatory effects of silymarin in beta- thalassemia
major are currently under further investigation in a double
blind clinical trial.
PMID: 16782543 [PubMed - indexed for MEDLINE] ----------------
------------------------------------------------------------=
---
J Vet Pharmacol Ther. 2007 Apr;30(2):132-8. Links
Bioavailability of a silybin-phosphatidylcholine complex in
dogs. Filburn CR, Kettenacker R, Griffin DW. Veterinary
Science Division, Nutramax Laboratories, Inc., Edgewood, MD
21040, USA.
Liver dysfunction often is associated with an imbalance in the
production and removal of free radicals derived from oxygen
and nitrogen and has been managed clinically with antioxidant
supplements, including silymarin extract derived from milk
thistle. The potential for enhanced bioavailability of a
phytosome complex containing phosphatidylcholine and silybin,
the primary active flavonolignan in silymarin extract, was
tested in dogs. A group of eight beagles (four males, four
females) were dosed orally with a silybin- phosphatidylcholine
complex (SPC) and a commercially available standardized
silymarin extract containing equivalent levels of silybin.
Dosing with the SPC resulted in Cmax, Tmax, and AUC0-24 h
values (mean+/-SD) for total silybin of 1310+/-880 ng/mL,
2.87+/-2.23 h, and 11,200+/-6520 ng.h/mL, respectively;
corresponding values for a standardized silymarin extract were
472+/-383 ng/mL, 4.75+/-2.82 h, and 3720+/-4970 ng.h/mL. A
second, separate group of beagles were also dosed with the
extract alone, yielding values of 449+/-402 ng/mL,
6=2E87+/-7.43 h, and 2520+/-2976 ng.h/mL. These data show that
a phytosome complex of phosphatidylcholine and silybin
markedly enhances bioavailability in dogs.
PMID: 17348898 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
---------------
<<snip>> Silybin administration significantly reduced
bothfunctional anomalies and the fibrotic process by chelating
desferrioxamine chelatable iron. <<snip>>
Alberto Masini1 , Daniela Ceccarelli2, Fabiola Giovannini2,
Giuliana Montosi2, Cinzia Garuti2 and Antonello Pietrangelo2
(1) Sezione di Patologia Generale, Dipartimento di Scienze
Biomediche, Universita di Modena, Modena, Italy
(2) Dipartimento di Medicina Interna, Universit=E0 di Modena,
Modena, Italy
Abstract Hepatic iron toxicity because of iron overload seems
to be mediated by lipid peroxidation ofbiological membranes
and the associated organelle dysfunctions. However, the
basicmechanisms underlying this process in vivo are still
little understood. Gerbils were dosed with weeklyinjections
of iron-dextran alone or in combination with sylibin, a
well-known antioxidant,by gavage for 8 weeks. A strict
correlation was found between lipid peroxidation and the
levelof desferrioxamine chelatable iron pool. A consequent
derangement in the mitochondrialenergy-transducing
capability, resulting from a reduction in the respiratory
chain enzymeactivities, occurred. These irreversible
oxidative anomalies brought about a dramatic drop intissue
ATP level. The mitochondrial oxidative derangement was
associated with thedevelopment of fibrosis in the hepatic
tissue. Silybin administration significantly reduced
bothfunctional anomalies and the fibrotic process by
chelating desferrioxamine chelatable iron. Iron - oxidant
stress - liver mitochondria (gerbil)
--------------------------------------------------------------
--------------=
-----
Alberto Masini Email: masini@unimo.it
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk