Sakaewan Ounjaijean

Effects of Green Tea on Iron Accumulation and Oxidative Stress in Livers of Iron-Challenged Thalassemic Mice

Liver is affected by secondary iron overload in transfusions dependent b-thalassemia patients. The redox iron can generate reactive oxidants that damage biomolecules, leading to liver fibrosis and cirrhosis. Iron chelators are used to treat thalassemias to achieve negative iron balance and relieve oxidant-induced organ dysfunctions. Green tea (GT) (Camellia sinensis) catechins exhibit anti-oxidation, the inhibition of carcinogenesis, the detoxification of CYP2E1-catalyzed HepG2 cells and iron chelation. The purpose of this study was to investigate the effectiveness of GT in iron-challenged thalassemic mice. Heterozygous BKO type-thalassemia (BKO) mice (C57BL/6) experienced induced iron overload by being fed a ferrocene-supplemented diet (Fe diet) for 8 weeks, and by orally being given GT extract (300 mg/kg) and deferiprone (DFP) (50 mg/kg) for a further 8 weeks. Liver iron content (LIC) was analyzed by TPTZ colorimetric and Perls staining techniques. Concentrations of liver reduced glutathione (GSH), collagen and malondialdehyde (MDA) were also measured. Dosages of the GT extract and DFP lowered LIC in the Fe diet-fed BKO mice effectively. The extract did not change any concentrations of liver glutathione, collagen and MDA in the BKO mice. Histochemical examination showed leukocyte infiltration in the near by hepatic portal vein and high iron accumulation in the livers of the iron-loaded BKO mice, however GT treatment lowered the elevated iron deposition. In conclusion, green tea inhibits or delays the deposition of hepatic iron in regularly iron-loaded thalassemic mice effectively. This will prevent the iron-induced generation of free radicals via Haber-Weiss and Fenton reactions, and consequently liver damage and fibrosis. Combined chelation with green tea would be investigated in beta-thalassemia patients with iron overload.

Epigallocatechin-3-gallate and Epicatechin-3-gallate from Green Tea Decrease Plasma Non-Transferrin Bound Iron and Erythrocyte Oxidative Stress

Beta-thalassemia patients suffer from secondary iron overload caused by increased iron absorption and multiple blood transfusions. Excessive iron catalyzes free-radical formation, causing oxidative tissue damage. Non-transferrin bound iron (NTBI) detected in thalassemic plasma is highly toxic and chelatable. Desferrioxamine and deferiprone are used to treat the iron overload, but many side effects are found. Epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) in green tea (GT) show strong antioxidant properties. We separated the EGCG and ECG from GT extract using an HPLC, and examined their iron-binding and free-radical scavenging activities. They bound Fe(3+) rapidly to form a complex with a predominant absorption at 560 nm. EGCG and ECG bound chemical Fe(3+) and chelated the NTBI in a time- and dose dependent manner. They also decreased oxidative stress in iron-treated erythrocytes. In conclusion, EGCG and ECG could be natural iron chelators that efficiently decrease the levels of NTBI and free radicals in iron overload.

IRON-CHELATING AND FREE-RADICAL SCAVENGING ACTIVITIES OF MICROWAVE-PROCESSED GREEN TEA IN IRON OVERLOAD

Secondary iron overload is found in β-thalassemia (thal) patients because of increased dietary iron absorption and multiple blood transfusions. Excessive iron catalyzes free-radical generation, leading to oxidative damage and vital organ dysfunction. Non-transferrin-bound iron (NTBI) detected in thalassemic plasma is highly toxic and chelatable. Though used to treat iron overload, desferrioxamine (DFO) and deferiprone (L1) also have adverse effects. Green tea (GT) shows many pharmacological effects, particularly antioxidative and iron-chelating capacities. This study was performed to investigate the ability of GT extracts to reduce plasma NTBI concentration and oxidative stress in vitro. The Fe3+ was found to bind to GT crude extract and form a complex. Green tea crude extract time- and dose-dependently decreased plasma NTBI concentration and counteracted the increase of oxidative stress in both Fe 2+-EDTA-treated human plasma and erythrocytes. Green tea is a bifunctional natural product that could be relevant for management of iron overload and oxidative stress.

Effect of green tea on iron status and oxidative stress in iron-loaded rats

Plasma non-transferrin bound iron (NTBI) is potentially toxic and contributes to the generation of reactive oxygen species (ROS), consequently leading to tissue damage and organ dysfunction. Iron chelators and antioxidants are used for treatment of thalassemia patients. Green tea (GT) contains catechins derivatives that have many biological activities. The purpose of this study was to investigate the iron-chelating and free-radical scavenging capacities of green tea extract in vivo. Rats were injected ip with ferric citrate together with orally administered GT extract (GTE) for 4 months. Blood was collected monthly for measurement of iron overload and oxidative stress indicators. Plasma iron (PI) and total iron-binding capacity (TIBC) were quantified using bathophenanthroline method. Plasma NTBI was assayed with NTA chelation/HPLC. Plasma malonyldialdehyde (MDA) was determined by using the TBARS method. Erythrocyte oxidative stress was assessed using flow cytometry. Levels of PI, TIBC, NTBI and MDA, and erythrocyte ROS increased in the iron-loaded rats. Intervention with GT extract markedly decreased the PI and TIBC concentrations. It also lowered the transferrin saturation and effectively inhibited formation of NTBI. It also decreased the levels of erythrocyte ROS in week 4, 12 and 16. Therefore, green tea extract can decrease iron in plasma as well as eliminate lipid peroxidation in plasma, and destroy formation of erythrocyte ROS in the rats challenged with iron. The bifunctional effects could be beneficial in alleviating the iron and oxidative stress toxicity. In prospective, these GTE activities should be further examined in thalassemic animals or humans.

Increase in non-transferrin bound iron and the oxidative stress status in epilepsy patients treated using valproic acid monotherapy.

OBJECTIVE This study aims to investigate the alteration of iron homeostasis and oxidative stress status in epilepsy patients treated with valproic acid (VPA) monotherapy. MATERIALS 24 epilepsy patients receiving VPA monotherapy (12 men, 12 women, age 27.5 ± 7.2 y) and 24 sex- and age-matched healthy volunteers were included in the study. METHODS The level of iron status parameters; serum iron, ferritin, transferrin saturation, non-transferrin bound iron (NTBI), serum level of trace elements (copper, zinc and selenium), concentration of antioxidant parameters, activities of antioxidant enzymes and level of lipid peroxidation product were determined. RESULTS NTBI was found in the patients although their other iron status parameters were normal. Levels of antioxidant parameters were decreased while activities of antioxidant enzymes were increased. Levels of serum MDA were significantly increased in patients with epilepsy. The daily dose of valproic acid associated was statistically significant: serum concentration of NTBI (r = 0.579; p = 0.003) and MDA (r = 0.465; p = 0.022). A positive correlation existed between NTBI and zinc (r = 0.522; p = 0.009). CONCLUSION According to our results, VPA treatment in patients with epilepsy contributes to the metabolism of iron, leading to the formation of NTBI and an increase in oxidative stress.

Micronutrients and Natural Compounds Status and Their Effects on Wound Healing in the Diabetic Foot Ulcer

The diabetic foot ulcer (DFU) is an invariably common complication of diabetes mellitus, it is also a significant cause of amputation as well as extended hospitalization. As most patients with DFU suffer from malnutrition, which has been related to improper metabolic micronutrients status, alterations can affect impaired wound healing process. Micronutrients and herbal remedies applications present a wide range of health advantages to patients with DFU. The purpose of this review is to provide current evidence on the potential effect of dietary supplementations such as vitamins A, C, D, E, magnesium, zinc, copper, iron, boron, and such naturally occurring compounds as Aloe vera, Naringin, and Radix Astragali (RA) and Radix Rehmanniae (RR) in the administration of lower extremity wounds, especially in DFU, and to present some insights for applications in the treatment of DFU patients in the future.

The effectiveness of iodine supplementation during pregnancies in geographical areas of high prevalence of iodine insufficiency

Abstract The objective of this study was to determine the effectiveness of routine iodine supplementation among pregnant women in areas of high prevalence of an iodine insufficiency, using WHO criteria to determine the iodine status. A longitudinal study was conducted on pregnant women attending antenatal care at a tertiary hospital. The urine iodine concentration was measured in the first trimester and after 150 μg of iodine supplementation in the third trimester. A total of 327 pregnant women met the inclusion criteria with a complete follow-up. The prevalence of an iodine insufficiency was significantly lower in the third trimester, when compared to the first trimester (21.41% vs 55.35%, p < .001). However, 21.4% of cases still had an iodine insufficiency and 35.17% had an ‘above-requirement’ in the third trimester. In the areas of high prevalence of iodine insufficiency, an iodine supplementation significantly reduces the number of women with insufficiency; however, it was associated with unnecessarily high UICs, leading to the risk of excess iodine. Impact statement What is already known on this subject: Iodine insufficiency is highly prevalent in many geographical areas. Half of the pregnant women in the northern part of Thailand had an iodine insufficiency in the first trimester. What do the results of this study add: Iodine supplementation (daily 150-mcg of potassium iodide) could significantly reduce the number of women with the insufficiency. About one-fifth of women still had an iodine insufficiency in spite of iodine supplementation. Universal supplementation could be associated with unnecessarily high UICs, potentially at risk of iodine excess. What are the implications of these findings for clinical practice and/or further research: Physicians should guard against the occurrence of adverse effect from an iodine excess when there is routine iodine supplementation for pregnant women. Further study is required to establish the best strategy for an iodine supplementation in pregnancy.

Higher Level of Chicken Consumption Associated With Less Severe Venous Disease

The aim of this study was to investigate the impact of various food intake in patients with varicose veins. A cross-sectional study was conducted between December 2012 through November 2014. Patients at the outpatient department 101 at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, who were older than > 18 years were invited to participate in this study. The severity of varicose veins was divided into 2 groups according to CEAP (clinical, etiological, anatomical, and pathophysiological) classification: mild type of venous disease (C0-C2) and severe type of venous disease (C3-C6). Patients were interviewed about their demographic data and frequency of meat consumption for varicose veins using Vein Consult Program (VCP). A total of 558 eligible outpatients were recruited for the study. Most patients were female (78.9%) and aged >50 years (47.1%). Seventeen out of 558 patients were diagnosed with high severity of venous disease (3.0%). Remarkably, significantly higher body weight (73.8 ± 13.9 vs 58.4 ± 11.2 kg, P = .000) and body mass index (28.8 ± 4.4 vs 23.3 ± 3.9 kg/m2, P = .000) was found in patients with severe types of venous disease compared with the mild group. Unexpectedly, only chicken intake demonstrated the different association with varicose veins (P = .022). Patients with severe venous disease showed lower frequency of chicken consumption. The results suggested an association of chicken consumption with a reduced chance of developing varicose veins.