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10-31-2006, 06:22 PM | #1 | |||
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Senior Member
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http://www.cdfin.iastate.edu/update/...5/project5.htm
Title: Neuroprotective Effect of Phytic Acid on Parkinson's Disease Investigators: Manju B. Reddy, Ph.D., Department of Food Science & Human Nutrition Anumantha G. Kanthasamy, Ph.D.,Department of Biomedical Sciences Type of Project: Renewal Overall Objective and Specific Aims: The overall objective of this study is to determine the therapeutic effect of phytic acid in preventing the neurodegeneration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropryidine (MPTP)-induced Parkinson's Disease (PD). We will specifically test for: Protective effect of phytic acid and its metabolites on cell death using a cell culture model Protective effect of phytic acid given orally at therapeutic doses in a mouse model PROGRESS REPORT: A Graduate student has been identified in the interdepartmental toxicology program this fall and currently she is getting training under Dr. Kanthasamy for behavioral, neurochemical, and neuropathalogical indicators of PD. JUSTIFICATION AND BACKGROUND: 1. Hypothesis: We hypothesize that phytic acid at therapeutic doses will protect against PD by preventing MPTP-induced neurodegeneration. This hypothesis is based on phytic acid's antioxidant and metal chelating properties (Graf and Eaton, 1990). 2. Rationale and Related Work: Parkinson's disease is characterized by a selective degeneration of dopaminergic neurons in the substantia nigra, resulting in irreversible motor dysfunction. The cardinal symptoms of PD include resting tremor, bradykinesia, and rigidity. This debilitating neurodegenerative disorder affects more than 1% of the US population over 50 years of age, and causes an estimated economic obligation of $25 billion annually (Scheife et al, 2000). Recent research interest has been directed to understand the pathogenesis of the disease as well as neuroprotective therapy. There have been many developments in the area of dopamine replacement strategies to neutralize the motor deficits resulting from the degeneration of dopaminergic neurons. These developments, however, are limited to symptomatic relief. Other limitations of these approaches include drug tolerance, drug-induced involuntary movements, and most importantly, dopamine therapy is ineffective in attenuating the progression of the illness. Therefore, alternate therapeutic strategies are warranted in identifying novel neuroprotective agents that effectively prevent the progression of the neurodegenerative process. 3. Related Work: Body iron concentration generally increases with age including brain iron content. Substantia nigra has about 20 ng/mg iron during the first year of life and increases to 200 ng/mg by the fourth decade (Zeccal et al, 2001). The role of iron in PD has recently gained attention because excessive iron accumulation in substantia nigra was found in postmortem brains from Parkinson's patients (Berg el al, 2002). The central role of iron in the pathogenesis of PD is by its involvement in oxygen free- radical production. Brain tissues are rich in polyunsaturated fatty acids, thus they are especially vulnerable to free radical mediated lipid peroxidation (Schafer et al, 2000). Because of association of excess iron and PD with age, we can speculate that iron has a definite role in PD development or progression. Although the alteration in brain iron pathways are discussed in relevance to PD, whether that is a cause or effect, is still obscure (Berg et al, 2001). In Parkinson's and Alzheimer's disease there is a disruption in the iron metabolism, such that there is an accumulation of iron in senile plaques and altered distribution of iron transport and storage proteins. These diseases are associated with elevated brain iron concentrations relative to the iron storage protein, ferritin. Ferritin, the primary nonheme iron storage protein, is believed to keep iron in a non-reactive form, where it can not promote redox reactions. Therefore ferritin could protect tissues against iron-catalyzed oxidative damage (Kaur et al, 2003). A rise in iron concentrations without concomitant change in ferritin provides "free iron" for free radical generation (Berg et al, 2001; Bishop et al, 2002). Selective cell death in the substantia nigra brain region is associated with oxidative stress, which may be exacerbated by the presence of excess iron. It is well know that iron is involved in the Haber-Weiss reaction in producing ·OH production, which is the most reactive oxygen species (ROS), damaging cells and causing many diseases. O2- + Fe3+ ® Fe2+ + O2 Fe2+ + H2O2 ® Fe3+ + ·OH + OH- Oxidative stress causing cell damage, including apoptosis, may play a prominent role in neurological degeneration associated with PD (Jenner and Olanow, 1996; Fahn, 1996; Burke et al, 1998; Kaul et al, 2003). Research on the use of antioxidants, free radical scavengers, and inducers of cellular antioxidant systems as therapeutic adjuncts in the treatment of PD continues to provide hope towards more effective therapies that not only treat symptoms, but also might slow the process of neurodegeneration. Based on this evidence, antioxidants are thought to have a great potential as therapeutic agents for treatment in the early stages of PD. For example, co-enzyme Q10 has recently been shown to have a protective effect against PD (Kanthasamy et al, 2001). In addition, estrogens, at endogenous concentrations or at pharmacological doses, are shown to offer neuroprotection in PD and other neurodegenerative disorders such as Alzheimer's disease. Dluzen and colleagues (1996) have found that dopaminergic toxicity induced by MPTP in ovarectomized female mice or rats can be attenuated by exogenous estrogen administration. Iron chelation via either transgenic expression of the iron-binding protein ferritin or oral administration of the metal chelator clioquinol (CQ) reduced the susceptibility to the MPTP for inducing PD, suggesting that iron chelation may also be an effective therapy for prevention and treatment of the disease (Kaur et al, 2003). Phytic acid (myo-inositol hexakiphosphate) is a food component that is considered an antinutrient by virtue of its ability to chelate divalent minerals and prevent their absorption (Reddy et al, 1996). Its unique chelating action with iron provides phytic acid with antioxidant characteristics. Phytic acid was shown to inhibit ·OH formation and decrease lipid peroxidation catalyzed by iron and ascorbate in human erythrocytes (Graf and Eaton, 1990). This suppression of iron-catalyzed oxidative reactions was suggested by the phytic acid's ability to form a unique chelate with Fe(III) occupying all of the coordinating sites (Graf et al,1984). Phytic acid's antioxidant ability in vivo is not clear, but in our study we showed a reduction of 60% in lipid peroxidation and 48% in liver iron stores with dietary phytic acid in a genetically overloaded-mouse model (Reddy and Guo, 2000). Recently, we also showed in a human study that feeding phytic acid containing soy protein for 6-weeks to postmenopausal women reduced body iron stores significantly compared with the low-phytic acid soy protein (Barwick et al, 2003). These results together suggest that phytic acid may have a protective effect in alleviating the iron- induced oxidative stress. Interestingly, phytic acid may influence oxidative stress independent of its hydroxyl radical inhibiting characteristics. It may alter cell signaling pathways (Shamsuddin et al, 1997) or may influence the activity and expression of key enzymes in the antioxidant defense system, which detoxifies the ROS. Our previous data support this hypothesis because liver catalase concentration increased significantly after feeding phytic acid in the diet for 10 weeks to iron-overloaded mice (Reddy and Guo, 2000). Based on the positive effect of iron chelators and antioxidants on PD and the antioxidant property and iron chelating ability of phytic acid, we hypothesize that phytic acid may protect against the neurodegeneration associated with PD. We would like to test this hypothesis at therapeutic doses based on the cancer prevention rat studies (Ullah et al, 1990) and human studies to treat idiopathic hypercalcuria (Henneman et al, 1958) with phytic acid. The results of this study will be useful to possibly develop phytic acid as a therapeutic nontoxic iron chelator for ameliorating the extent of oxyradical-induced damage as was seen in an ischemia heart- perfusion injury model (Rao et al, 1991). To date, no such studies have been reported in PD. This project defines work that is within the long-term goals of the investigators regarding their specialty areas of iron-induced oxidative stress and neuroprotection. |
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10-31-2006, 06:32 PM | #2 | |||
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Senior Member
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http://www.phytochemicals.info/phyto...hytic-acid.php
Phytochemical: Phytic acid Synonyms: Inositol-phosphate Description: In plants phytic acid is the principal store of phosphate. Phytic acid is a natural plant antioxidant. Distribution: Phytic acid can be found in most grains, seeds and beans. Rich sources of phytic acid are wheat bran and flaxseed (3 % phytic acid). Action of Phytic acid: Phytic acid has been considered as an anti-nutritional component in cereals, seeds and beans. Research has traditionally focused on its structure that gives it the ability to bind minerals, proteins and starch, and the resulting lower absorption of these elements. However, resent research have shown that phytic acid has many health promoting effects. Phytic acid has antioxidant, anticarcinogenic, hypocholesterolemic and hypolipidemic effects. In animal studies phytic acid showed a protective action in carcinogenesis. This action could be explained by its mineral chelating potential. Phytic acid lowers blood glucose response by reducing the rate of starch digestion and slowing the gastric emptying. Phytic acid releases inositol that during digestion. Although inositol is not an essential nutrient it might reduce depressions. (on the web site Carolyn posted giving one access to lectures presented at the Young parkinson's conference, the physician who spoke about supplements/vitamins and nutrition, Dr. David Heydrick,{ had PD from age 40} recommended one take evening primrose oil with flax seeds--the primrose oil was for Omega 6 intake and flax seed was to stop the pathway of omega 6's to inflammatory pathways....anyone here take flax seed? I have read that one should buy the seed and grind it oneself for ultimate absorption) address for YOPD conference from carolyn's posting: http://event.netbriefings.com/event/...e/register.cgi |
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10-31-2006, 11:14 PM | #3 | ||
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Junior Member
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hi,
i believe dr heydrick said that sesame seeds should be taken with the primrose. i dont take flax seeds but the flax oil we eat on salads, rice, and pasta. |
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11-01-2006, 07:17 AM | #4 | ||
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New Member
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I do flax seed & primrose oil - reccommneded by a MD that also uses ayurvedic herbs-- He put me on an anti inflamatory diet & many supplements.
Felt better winthin a week, more energy, no tremor (tremor has not been my dominant symptom) Did diet for 3 months -- whenever I "cheated" usually would become more symptomatic . After 3 months you are supposed to slowly add back food to see how they affect you. I don't feel as well as I did this past summer but better than a year ago . I'm still follwing the diet somewhat. & coincendentally my chiropractor recently suggested inositol supplements to stabilize blood sugar I've been lurking for some time-- this is my first post. I've learned alot from you all. Thanks. DX 03, disability 05, MEDS stalevo 50 3x, requip 1 mg 3x |
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11-01-2006, 08:53 AM | #5 | |||
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Senior Member
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hi oyster, you are correct--it is sesame seeds dr. heydrick suggests to take with evening primrose oil. seems i became too excited about a "coincidence" and misremembered the supplement. thanks for the correction--what did you think of dr.heydrick's lecture? lots of info there on supplements and vitamins. madelyn
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11-01-2006, 09:49 AM | #6 | ||
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particularly as I just had a chat with an esteemed bio-chemist who is currently pursuing the excess iron factor in pd (& other) brains. He recommends giving blood regularly (every other month) as a means of reducing iron.
I like the flax seed approach much better. I use it - and will be sure to make it a regular -ie daily - addition to me diet. Thanks! IBby |
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