Iron Buildup Research Articles

British Society for Haematology guidelines for the management of adult myelodysplastic syndromes.

British Society for Haematology guidelines for the management of adult myelodysplastic syndromes.

Activation of Autophagy in Models of SF3B1 Mutant MDS

Background:SF3B1 is a key pre-mRNA splicing factor that is abundantly expressed in normal erythroid cells and whose mutation has been linked with high frequency to myelodysplastic syndromes with ringed sideroblasts (MDS with RS) implying that this gene may be an important driver of the pathogenesis of this subtype. Given that MDS with RS is characterized by ineffective erythropoiesis, we previously investigated the link between SF3B1 aberrations and the regulation of pathways that control erythroid maturation and iron homeostasis. Indeed, knockdown of SF3B1 led to significant impairment of the growth of erythroid cells and delayed erythroid differentiation. MDS erythroid cells were unable to properly process iron, resulting in its accumulation in mitochondria. Iron build-up inhibited the proliferation of erythroid progenitors and induced mitochondrial DNA-damage. During erythroid maturation, autophagy plays critical roles in the clearance of damaged mitochondria and maintaining iron homeostasis. Knockout of the essential autophagy gene, Atg7 leads to anemia due to a delayed clearance of mitochondria with a consequent increase in iron levels, ultimately resulting in increased reactive oxygen species formation. As such, we set out to determine if autophagy upregulation alleviates oxidative stress and thereby increases erythropoiesis in MDS with RS.Methods: Transmission electron microscopy (TEM) was performed to examine the cytoplasmic vacuolization, autophagosome content, and morphology of vacuoles and mitochondria in SF3B1 mutant (SF3B1MUT) vs. wild-type (SF3B1WT) cells. Immunoblotting was used to detect microtubule-associated protein 1 light chain 3 (LC3B), p62, and cathepsin D (marker of autophagic degradation). Whole exome sequencing (WES) was used to detect somatic alterations in autophagy genes and RNA-Sequencing and qPCR were conducted to evaluate differences in mRNA expression levels of autophagy genes. A missense mutation in SF3B1 resulting in K700E amino-acid substitution was introduced using EGE-CRISPR/Cas9-stimulated homology-mediated repair to generate heterozygous K562 cells expressing K700E.Transgenic heterozygous SF3B1 mice were used as an in vivo model. Temsirolimus (CCI-779), an mTOR inhibitor with autophagy-inducing properties, was tested in vitro and in vivo.Results: We identified numerous autophagosomes, double-membraned autophagic vacuoles, and single-membrane cytoplasmic structures in SF3B1MUTvs. SF3B1WT cells. LC3B protein was higher in primary SF3B1MUTvs. SF3B1WT cells. WES did not detect any somatic mutations in autophagy genes in the patients analyzed by TEM. RNA-Sequencing and qPCR showed that primary SF3B1MUT MDS with RS cells displayed increased expression levels of key genes of the ATG-autophagy pathway: [ATG2A/B, ATG3, ATG5 (FC=2), ATG9, (FC=5); P=.05], serine/threonine kinases [ULK1 (FC=2), ULK3 (FC=4); P=.05], and cathepsins [CTSB/D (FC=2), CTSE (FC=6); P=.01]. CRISPR/Cas9 K700E cells showed high autophagosome counts, increased basal expression of LC3B protein, and a 2-fold increase in autophagy genes (ATG5, ATG7, ULK1) compared to parental cells. Treatment with temsirolimus (10-100 nM) for 24 hours induced growth inhibition (IC50, 50 nM), enhanced the amount of autophagosomes containing degraded organelles, increased the percentage of dividing CD71+ cells and induced a 2-fold increase in LC3B in CRISPR/Cas9 K700E cells compared to parental cells. Temsirolimus (10 mg/kg i.p. 5d/wk) administered for two weeks to 6-8-month-old transgenic SF3B1 heterozygous mice (N=20) induced autophagy by increasing the number of autophagosomes and autophagolysosomes containing entrapped mitochondria, increased hemoglobin (7.5 vs. 6.6 g/dL; P=.05), and doubled the percentage of CD71+ erythroid cells (5-10%) in temsirolimus-treated vs. untreated SF3B1 mice.Conclusions: Basal autophagy is significantly upregulated in SF3B1MUT cells. Further stimulation of autophagic activity using FDA approved pathway-activating drugs may improve rates of erythrocyte production by SF3B1MUT clones and thus improve control of anemia in MDS with RS cases. DisclosuresAdvani:Takeda/ Millenium: Research Funding; Pfizer: Consultancy. Kelly:Pharmacyclics: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Jannsen: Honoraria. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees. Carew:Millenium/ Takeda: Research Funding.

Pathology of Hepatic Iron Overload

Pathology of Hepatic Iron Overload

Variables associated with subclinical atherosclerosis among rheumatoid arthritis patients of Gulf Cooperative Council countries

Objectives:To evaluate the cardiovascular disease (CVD) as demonstrated by carotid intima-media thickness (cIMT) and the cluster risk factors of CVD including traditional and non-traditional, urinary functions, iron buildup, and hemorheology in rheumatoid arthritis (RA) patients of Gulf Cooperative Council (GCC) countries.Methods:Carotid intima-media thickness was obtained from 216 RA patients, free of atherosclerotic diseases. The correlation between cIMT and the possible CVD risk factors was carried out using regression analysis.Results:The mean cIMT was observed as 0.58±0.11 mm. Mean age was 48±13 years. Univariate analysis revealed a positive association (p<0.05) between cIMT and age, body mass index, systolic blood pressure (SBp), and diastolic blood pressure, c-reactive protein (CRP), triglycerides (TG), low-density lipoprotein (LDL), erythrocyte sedimentation rate (ESR), hemoglobin (Hb), hematocrit (Hct), mean cell volume, platelet, monocytes, eosinophils, ferritin, creatinine, and uric acid. Negative relationship was observed between cIMT and glomerular filtration rate (GFR), transferrin, and high-density lipoprotein. Multiple linear regression analysis exhibited a positive association between cIMT and the age, LDL, eosinophil, SBp, and the ESR, whereas, negative connection with the GFR and transferrin.Conclusion:In this study, we found that the eosinophils, and low transferrin, are the potential candidates for the CVD risk factors in RA patients. Fasting blood glucose level was also observed to be a significant risk factor in diabetic as well as non-diabetic RA. The remaining CVD risk factors in RA patients of GCC countries including older age, high SBp, ESR, LDL, and low GFR were similar to the international population.

Serum markers of iron metabolism in chronic hepatitis C virus infections

Background Hepatitis C virus (HCV) infection is a common cause of chronic hepatitis, which leads to cirrhosis of the liver and hepatocellular carcinoma. Chronic hepatitis can cause iron buildup in the liver and result in liver injury. The major iron metabolism regulator, the hepatic hormone hepcidin, inhibits iron absorption and recycling, and as hepcidin is suppressed by the virus, it contributes to the pathogenesis of the liver. Aim To assess serum iron markers in patients with chronic hepatitis C (CHC) as opposed to people who are healthy and a summary of interactions of HCV and iron overload. Patients and methods This case–control study was performed on 30 hepatitis C-infected Egyptian patients (group I) and 15 apparently healthy control (group II). Routine laboratory investigations, as well as serum hepcidin and iron marker assessments were performed. Results Throughout this study, the serum hepcidin level in patients significantly decreased relative to the control group (P&lt;0.001). The patients showed significantly higher serum iron, transferrin saturation, alanine aminotransferase, and aspartate aminotransferase compared with the control group (P&lt;0.001). Serum albumin in patients’ group was considerably decreased in comparison with the control (P&lt;0.05). There was a highly statistically significant lower platelet count value in patients compared with the control group (P&lt;0.001). The interaction between hepcidin and iron, transferrin, and alanine aminotransferase is significantly negative. Conclusion Hepatic iron deposition is a joint feature in patients with CHC. Chronic HCV infection may reduce serum hepcidin, which may lead to iron overload in these patients. So hepcidin is a surrogate marker for evaluation of iron overload in patients with CHC.

Pathogenesis, Diagnostics, and Treatment of Hereditary Haemochromatosis: A 150 Year-Long Understanding of an Iron Overload Disorder

Haemochromatosis is an iron overload disorder that can be inherited or acquired and when diagnosis is delayed, disease progression and death can occur. Iron overload was first described by the French internist Armand Trousseau in 1865 in an article on diabetes in which alterations in skin pigmentations were reported. Some years later, the German pathologist Friedrich Daniel von Recklinghausen coined the term ‘haemochromatosis’ for a metabolic disorder characterised by excess deposition of iron in the tissue. This disorder affects 1 in 200 subjects of Caucasians of Northern European descent. The systemic excess iron build-up condition quickly gained an intense clinical interest. Haemochromatosis can lead to severe pathological symptoms in multiple organs, including the liver, bones, spleen, heart, pancreas, joints, and reproductive organs. With the progress of the disease, hepatic damage predominates. Polymorphisms in several independent genes can lead to haemochromatosis. However, the most widely known haemochromatosis-associated and studied ones are genetic variants in the HFE gene, located on the short arm of human chromosome 6. Early detection and phlebotomy prior to the onset of fibrosis/cirrhosis can reduce morbidity and normalise life expectancy. Consequently, phlebotomy has been accepted for decades as a standard treatment for the reduction of iron load. Nowadays, other methods, such as erythrocytapheresis, therapeutic application of iron chelators and proton pump inhibitors, or hepcidin-targeted therapy, are discussed as alternative personalised treatments of hereditary haemochromatosis. This review focusses on the pathogenesis, diagnosis, and therapy of haemochromatosis.

A study of the sources, human health implications and low cost treatment options of iron rich groundwater in the northeastern coastal areas of KwaZulu-Natal, South Africa

The groundwater of the northeastern coastal region of KwaZulu-Natal province of South Africa is characterized by high iron content. When the iron rich groundwater is pumped out to the surface, the water forms a precipitate of solid Fe-oxyhydroxide giving the water a cloudy reddish color. This condition is caused by the interaction of Fe2+in the groundwater with atmospheric oxygen. Since this water is unfit for many purposes including domestic use, the local community's water supply is being highly affected. An investigation was undertaken to identify the source of high iron within the Zululand plain groundwater system, the health implications and affordable treatment options in order to make the water suitable for use. The results of the investigation show that the concentration of iron in the groundwater reaches 13mg/L. The measured groundwater EC ranges from 124 to 1060μS/cm, pH ranges from 5 to 8 and redox potential (Eh) ranges from +87 to −89mV indicating both local oxidizing and reducing conditions. The results further show that the groundwater in the area is a fresh water system dominated by a Na–Cl hydrochemical facies indicating strong maritime influences. High iron concentration in water increases growth of unwanted bacteria forming slimy coatings in water pipes and when consumed excessively, it can lead to the build-up of iron in the body resulting into iron stores (high serum ferritin) which may be linked to diseases such as diabetes, heart disease, cancer and kidney problems. High residual content of iron in drinking water is also responsible for the unaesthetic nature of the water such as the metallic taste, discoloration and unpleasant smell of the water. Anaerobic groundwater conditions and the pH range observed during the investigation along with the presence of ferricrete and pyrite rich layers are responsible for the high concentrations of iron (II). An affordable groundwater treatment method based on aeration is recommended in order to safeguard community health, avoid expensive alternative water supply schemes and improve the negative perceptions of communities towards groundwater

Haptoglobin genotype and its role in determining heme-iron mediated vascular disease

Haptoglobin (Hp) is a hemoglobin (Hb) binding protein whose major function is to prevent heme-iron mediated oxidation. The polymorphic nature of the Hp gene results in varying levels of antioxidant function associated with the protein products. Multiple clinical studies have now determined that the Hp 2-2 genotype is associated with an increased risk of developing vascular complications in patients suffering from diabetes. The mechanism for this phenomenon is a decrease in antioxidant capability associated with the Hp 2-2 protein. Specifically, heme iron associated with the Hp2-2/Hb complex is more redox active than other Hp type complexes and has been shown in a number of systems to lead to increased levels of oxidative stress in the form of oxidized lipids and decreased lipoprotein function. In addition, Hp 2-2/Hb complexes are cleared less efficiently from the circulation, leading to a buildup of iron in the plasma and in tissues. Recent analyses from clinical studies utilizing vitamin E treatment have shown beneficial results specifically in the diabetic Hp 2-2 genotype population. The use of vitamin E in the treatment of Hp 2-2 diabetics has the potential to greatly reduce medical costs and improve quality of life in the ever-growing diabetic population.

Bmp6 Regulates Retinal Iron Homeostasis and Has Altered Expression in Age-Related Macular Degeneration

Iron-induced oxidative stress causes hereditary macular degeneration in patients with aceruloplasminemia. Similarly, retinal iron accumulation in age-related macular degeneration (AMD) may exacerbate the disease. The cause of retinal iron accumulation in AMD is poorly understood. Given that bone morphogenetic protein 6 (Bmp6) is a major regulator of systemic iron, we examined the role of Bmp6 in retinal iron regulation and in AMD pathogenesis. Bmp6 was detected in the retinal pigment epithelium (RPE), a major site of pathology in AMD. In cultured RPE cells, Bmp6 was down-regulated by oxidative stress and up-regulated by iron. Intraocular Bmp6 protein injection in mice up-regulated retinal hepcidin, an iron regulatory hormone, and altered retinal labile iron levels. Bmp6(-/-) mice had age-dependent retinal iron accumulation and degeneration. Postmortem RPE from patients with early AMD exhibited decreased Bmp6 levels. Because oxidative stress is associated with AMD pathogenesis and down-regulates Bmp6 in cultured RPE cells, the diminished Bmp6 levels observed in RPE cells in early AMD may contribute to iron build-up in AMD. This may in turn propagate a vicious cycle of oxidative stress and iron accumulation, exacerbating AMD and other diseases with hereditary or acquired iron excess.

Accumulation of oxidative DNA damage in brain mitochondria in mouse model of hereditary ferritinopathy

Tissue iron content is strictly regulated to concomitantly satisfy specialized metabolic requirements and avoid toxicity. Ferritin, a multi-subunit iron storage protein, is central to maintenance of iron homeostasis in the brain. Mutations in the ferritin light chain (FTL)-encoding gene underlie the autosomal dominant, neurodegenerative disease, neuroferritinopathy/hereditary ferritinopathy (HF). HF is characterized by progressive accumulation of ferritin and iron. To gain insight into mechanisms by which FTL mutations promote neurodegeneration, a transgenic mouse, expressing human mutant form of FTL, was recently generated. The FTL mouse exhibits buildup of iron in the brain and presents manifestations of oxidative stress reminiscent of the human disease. Here, we asked whether oxidative DNA damage accumulates in the FTL mouse brain. Long-range PCR (L-PCR) amplification-mediated DNA damage detection assays revealed that the integrity of mitochondrial DNA (mtDNA) in the brain was significantly compromised in the 12- but not 6-month-old FTL mice. Furthermore, L-PCR employed in conjunction with DNA modifying enzymes, which target specific DNA adducts, revealed the types of oxidative adducts accumulating in mtDNA in the FTL brain. Consistently with DNA damage predicted to form under conditions of excessive oxidative stress, detected adducts include, oxidized guanines, abasic sites and strand breaks. Elevated mtDNA damage may impair mitochondrial function and brain energetics and in the long term contribute to neuronal loss and exacerbate neurodegeneration in HF.

Impact of gene patents and licensing practices on access to genetic testing for hereditary hemochromatosis

Hereditary hemochromatosis is an iron metabolism disorder that leads to excess iron buildup, especially in the heart, liver, and pancreas. Mutations in the HFE gene are the single most common cause of hereditary hemochromatosis, which can be treated effectively if diagnosed early. Patents cover the HFE gene, related proteins, screening methods, and testing kits. Most initial testing for hereditary hemochromatosis is biochemical, but HFE deoxyribonucleic acid testing or genotyping is used to confirm a diagnosis of inherited hemochromatosis. Concerns over patents covering HFE testing emerged in 2002, when scholars argued that exclusive licensing and the patent-enabled sole provider model then in place led to high prices and limited access. Critics of the sole provider model noted that the test was available at multiple laboratories before the enforcement of patents. By 2007, however, Bio-Rad Limited, acquired the key intellectual property and sublicensed it widely. In part because of broad, nonexclusive licensing, there are now multiple providers and testing technologies, and research continues. This case study illustrates how both changes in intellectual property ownership and evolving clinical utility of HFE genetic testing in the last decade have effected the licensing of patents and availability of genetic testing.

Deferoxamine Reduces Intracerebral Hematoma-Induced Iron Accumulation and Neuronal Death in Piglets

Our previous studies found that deferoxamine reduces intracerebral hemorrhage (ICH)-induced brain injury in rats. The current study examined whether deferoxamine reduces brain injury in a piglet ICH model. Pigs received an injection of autologous blood into the right frontal lobe. Deferoxamine (50 mg/kg, IM) or vehicle was administered 2 hours after ICH and then every 12 hours up to 7 days. Animals were killed 3 or 7 days later to examine iron accumulation, white matter injury, and neuronal death. ICH resulted in development of a reddish perihematomal zone, and iron accumulation, ferritin upregulation, and neuronal death within that zone. Deferoxamine reduced the perihematomal reddish zone, white matter injury, and the number of Perls', ferritin, and Fluoro-Jade C-positive cells. Iron accumulation occurs in the piglet brain after ICH. Deferoxamine reduces ICH-induced iron buildup and brain injury in piglets.

Iron Overload and Iron Chelation Therapy in Pediatric Patients

Iron overload is an unfortunate clinical consequence of repeated blood transfusions that can cause significant organ damage, morbidity, and mortality in the absence of proper treatment. Pediatric patients with transfusion-dependent pathologies face the additional risk of growth failure and poor sexual development owing to iron build-up in the anterior pituitary gland. Iron chelation therapy is necessary for the removal of excess iron, but treatment efficacy and success are highly dependent on patient compliance. Deferoxamine is a well-established but inconvenient therapy requiring parenteral administration over extended periods of time. Patient compliance can be improved with use of the oral iron chelators deferasirox and deferiprone. Long-term data have shown deferasirox to have a good safety and efficacy profile in pediatric patients.

Iron Overload and Iron Chelation Therapy in Pediatric Patients

Iron overload is an unfortunate clinical consequence of repeated blood transfusions that can cause significant organ damage, morbidity, and mortality in the absence of proper treatment. Pediatric patients with transfusion-dependent pathologies face the additional risk of growth failure and poor sexual development owing to iron build-up in the anterior pituitary gland. Iron chelation therapy is necessary for the removal of excess iron, but treatment efficacy and success are highly dependent on patient compliance. Deferoxamine is a well-established but inconvenient therapy requiring parenteral administration over extended periods of time. Patient compliance can be improved with use of the oral iron chelators deferasirox and deferiprone. Long-term data have shown deferasirox to have a good safety and efficacy profile in pediatric patients.

Iron homeostasis and toxicity in retinal degeneration

Iron is essential for many metabolic processes but can also cause damage. As a potent generator of hydroxyl radical, the most reactive of the free radicals, iron can cause considerable oxidative stress. Since iron is absorbed through diet but not excreted except through menstruation, total body iron levels buildup with age. Macular iron levels increase with age, in both men and women. This iron has the potential to contribute to retinal degeneration. Here we present an overview of the evidence suggesting that iron may contribute to retinal degenerations. Intraocular iron foreign bodies cause retinal degeneration. Retinal iron buildup resulting from hereditary iron homeostasis disorders aceruloplasminemia, Friedreich's ataxia, and panthothenate kinase-associated neurodegeneration cause retinal degeneration. Mice with targeted mutation of the iron exporter ceruloplasmin have age-dependent retinal iron overload and a resulting retinal degeneration with features of age-related macular degeneration (AMD). Post mortem retinas from patients with AMD have more iron and the iron carrier transferrin than age-matched controls. Over the past 10 years much has been learned about the intricate network of proteins involved in iron handling. Many of these, including transferrin, transferrin receptor, divalent metal transporter-1, ferritin, ferroportin, ceruloplasmin, hephaestin, iron-regulatory protein, and histocompatibility leukocyte antigen class I-like protein involved in iron homeostasis (HFE) have been found in the retina. Some of these proteins have been found in the cornea and lens as well. Levels of the iron carrier transferrin are high in the aqueous and vitreous humors. The functions of these proteins in other tissues, combined with studies on cultured ocular tissues, genetically engineered mice, and eye exams on patients with hereditary iron diseases provide clues regarding their ocular functions. Iron may play a role in a broad range of ocular diseases, including glaucoma, cataract, AMD, and conditions causing intraocular hemorrhage. While iron deficiency must be prevented, the therapeutic potential of limiting iron-induced ocular oxidative damage is high. Systemic, local, or topical iron chelation with an expanding repertoire of drugs has clinical potential.

Comparative study of iron(III) separation from zinc sulphate–sulphuric acid solutions using organophosphorus extractants, OPAP and D2EHPA: Part II. Stripping

Iron(III) solvent extraction removal from zinc process solutions by OPAP (octylphenyl acid phosphate) and D2EHPA (di-(2-ethylhexyl)phosphoric acid) was studied from the standpoint of stripping with HCl such that a saleable waste-free iron product could be generated downstream using existing pyrohydrolysis technology. OPAP (0.95 F) at 20 °C was found to be an excellent extractant for the preparation of concentrated iron chloride strip solutions. Its major advantages included very low sulphate carry-over, reasonable zinc carry-over, very low chloride back-extraction, and economic iron build-up and acid balance when a ‘moderate strength’ HCl–FeCl 2 strip feed (3.38 N HCl–58.5 g/L Fe(II)–9.7 g/L Fe(III)) was used. Major drawbacks with D2EHPA were identified which included significant sulphate carry-over and ineffective stripping and hence, poor iron build-up (≪ 100 g/L) with the ‘moderate strength’ strip feed. OPAP exhibited lower chloride back-extraction than D2EHPA. High molar ratio values of back-extracted chloride and unstripped iron(III) suggest a predominance of Fe(III)–chloro complexes in D2EHPA. OPAP stripping with 4 N HNO 3 at 50 °C was found to be ineffective.

Sonographic Findings in Fetal Alpha Thalassemia Major

Alpha thalassemia major is an autosomal recessive disease found mostly in Southern Chinese and Southeast Asians. It is caused by deletion of alpha globin genes. Normally, there are four alpha genes. 1Some cases lead to lifelong dependence on transfusions, with iron buildup and shortened life duration. Depending on the number of genes affected, the fetus may die in utero or very soon after birth.2

Subdivision of Glacial Deposits in Southeastern Peru Based on Pedogenic Development and Radiometric Ages

The Cordillera Vilcanota and Quelccaya Ice Cap region of southern Peru (13°30′–14°00′S; 70°40′–71°25′W) contains a detailed record of late Quaternary glaciation in the tropical Andes. Quantification of soil development on 19 moraine crests and radiocarbon ages are used to reconstruct the glacial history. Secondary iron and clay increase linearly in Quelccaya soils and clay accumulates at a linear rate in Vilcanota soils, which may reflect the semicontinuous addition of eolian dust enriched in secondary iron to all soils. In contrast, logarithmic rates of iron buildup in soils in the Cordillera Vilcanota reflect chemical weathering; high concentrations of secondary iron in Vilcanota tills may mask the role of eolian input to these soils. Soil-age estimates from extrapolation of field and laboratory data suggest that the most extensive late Quaternary glaciation occurred >70,000 yr B.P. This provides one of the first semiquantitative age estimates for maximum ice extent in southern Peru and is supported by a minimum-limiting age of ∼41,520 14C yr B.P. A late glacial readvance culminated ∼16,650 cal yr B.P. in the Cordillera Vilcanota. Following rapid deglaciation of unknown extent, an advance of the Quelccaya Ice Cap occurred between ∼13,090 and 12,800 cal yr B.P., which coincides approximately with the onset of the Younger Dryas cooling in the North Atlantic region. Moraines deposited <394 cal yr B.P. in the Cordillera Vilcanota and <300 cal yr B.P. on the west side of the Quelccaya Ice Cap correlate with Little Ice Age moraines of other regions.

Geochemical processes of iron and manganese in a seasonally stratified lake affected by coal-mining drainage in China

Lake water, pore water, and sediments were sampled in a seasonally stratified lake affected by coal-mining drainage. Contrasting geochemical processes of iron and manganese in summer were investigated by studying the seasonal distributions of iron and manganese species in the water column, pore water, and sediments. The results show that iron buildup in the water during summer was mainly from the gradual dissolution of particulate matter due to the pH decrease, whereas manganese oxide reduction and manganese-bound carbonate dissolution near the sediment–water interface were mainly responsible for manganese accumulation in the stratified hypolimnion. The geochemical processes of iron and manganese in the sediments during early diagenesis were also discussed in terms of the possible influence on the overlying water.

Estudio caso-control de marcadores de estrés oxidativo y metabolismo del hierro plasmático en la enfermedad de Parkinson

Increasingly growing evidence exists of the involvement of oxidative stress mechanisms in Parkinson's disease. Lower levels of GSH in the sustantia nigra, an increase in iron buildup, an increase in the byproducts of lipid peroxidation and alterations in the mitochondrial complex I have been described. However, few studies have been made of levels of antioxidants in the peripheral bloodstream and of the influence of the intake of nutrients on the development of this disease. In a group of 79 patients afflicted with idiopathic Parkinson's disease and a control group comprised of 107 subjects, compared by age, sex and place of residence, the lowered levels in the plasma of glutathione (GSH), malon dialdehyde (MDA), uric acid, tocophenol, beta-carotene, lycopene and different iron metabolism parameters were studied. Likewise, the intake of certain antioxidants was estimated based on a dietary survey. Significant differences (p < or = 0.001) were found in the plasma levels of GSH between cases (0.10 mumol/ml +/- 0.06) and controls (0.29 mumol/ml +/- 0.12). Likewise, the plasma levels of uric acid were lower (p < or = 0.05) in the cases (4.96 mg/ml +/- 1.96) than in the control groups (5.39 mg/ml +/- 1.13). No significant difference was found in the plasma levels of MDA, tocopherol, beta-carotene and lycopene. With regard to iron metabolism, significantly higher ferritine and transferrin values were found in the patients with EP than in the control group, showing a lower transferrin saturation percentage (p < or = 0.05). The iron showed no significant changes between cases and control groups. The results of this study support the possible involvement of oxidative stress in the pathogenesis of Parkinson's disease and reveal, in turn, alterations in some peripheral blood parameters in keeping with known findings in the sustantia nigra.