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Oral administration of 5-aminolevulinic acid induces heme oxygenase-1 expression in peripheral blood mononuclear cells of healthy human subjects in combination with ferrous iron.
Ito, H, Nishio, Y, Hara, T, Sugihara, H, Tanaka, T, Li, XK
European journal of pharmacology. 2018;:25-33
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Abstract
Heme oxygenase-1 (HO-1) is a major anti-inflammatory enzyme and a key regulator that induces immune tolerance through affecting the differentiation of dendritic cells. The aim of this study is to determine whether the combination of 5-aminolevulinic acid (ALA) and iron induces HO-1 expression in healthy human peripheral blood mononuclear cells (PBMC). The study was an open labeled, non-randomized, non-placebo-controlled trial using healthy male adults and consisted of three parts. Study A aimed to find the peak HO-1 expression at 0, 1, 2, 3, 4, 6, 8, 12, 16, and 24 h after administration. Study B aimed to examine HO-1 dose dependency at 150, 300, and 600 mg of ALA and the need for iron supplementation. Study C aimed to investigate HO-1 changes during a three-day, repetitive administration of ALA and iron. The combination of ALA 600 mg and sodium ferrous citrate (SFC) 942 mg upregulated HO-1 in PBMC at 8 h after administration while sole administration of ALA or SFC was unable to induce HO-1. HO-1 in blood myeloid and plasmacytoid dendritic cells was also upregulated with ALA+SFC. Clear dose dependency of ALA+SFC was not detected, and a slight tendency towards a cumulative effect of HO-1 after three-day, repetitive administration was observed. ALA, which is already approved for use in several countries as a diagnosis agent for cancer, has the potential to become a novel therapeutic drug for diseases stemming from unwanted immune response such as autoimmune diseases and the rejection response following organ transplantation.
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Response of urinary biomarkers of systemic oxidation to oral iron supplementation in healthy men.
Orozco, MN, Solomons, NW, Schümann, K, Friel, JK
Food and nutrition bulletin. 2012;(1):53-62
Abstract
BACKGROUND Urinary biomarkers are used in assessment of severe, clinical oxidative stress. Little is known, however, about their diagnostic value within the normative range. OBJECTIVE To evaluate the response of urinary thiobarbituric acid reactive substances (TBARS) and 8-hydroxy-2-deoxyguanosine (8-OHdG) as indicators of systemic oxidation in response to short-term oral iron and antioxidant supplementation. METHODS Five healthy adult men participated in the pilot study phase and 12 in the definitive intervention trial. For 7 days each, separated by 12-day washouts, the subjects received different treatment regimens, consisting of 120 mg of iron, 120 mg of iron in refined palm oil, and 120 mg of iron in palm oil combined with one of the two doses of Carotino Tocotrienol Carotene Mixed Concentrate (CTCMC). Creatinine-normalized urinary TBARS and 8-OHdG concentrations were quantified in samples taken from subjects with and without active supplementation. Temporal and correlative associations between TBARS and 8-OHdG were explored. RESULTS Daily intake of supplemental iron failed to produce any increment in urinary excretion of TBARS or 8-OHdG. However, a significant within-individual correlation between the urinary biomarkers was observed (Spearman r = 0.697, p < .0001, n = 466). Both doses of CTCMC significantly lowered urinary excretion of both oxidation indicators. CONCLUSIONS Despite the lack of effect of oral iron on the biomarkers of systemic oxidation, they show a strong and significant mutual association within the nonpathological range of oxidative stress in healthy male adults.
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Fortification iron as ferrous sulfate plus ascorbic acid is more rapidly absorbed than as sodium iron EDTA but neither increases serum nontransferrin-bound iron in women.
Troesch, B, Egli, I, Zeder, C, Hurrell, RF, Zimmermann, MB
The Journal of nutrition. 2011;(5):822-7
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Abstract
The absorption profile of iron fortificants may be a determinant of their ability to generate nontransferrin-bound iron (NTBI) and, thus, their potential safety. Ferrous iron may be absorbed more rapidly than chelated ferric iron, but differences at the fortification level cannot be distinguished with nonisotopically labeled serum iron curves. Using stable isotope appearance curves (SIAC) in serum, we measured iron absorption profiles from FeSO(4) with ascorbic acid (AA) and from NaFeEDTA, as well as the serum hepcidin and NTBI response following the meals. Healthy women (n = 16) were given 6 mg oral iron as labeled FeSO(4) and NaFeEDTA with a maize porridge using a crossover design. SIAC, NTBI, and serum hepcidin were measured over 8 h after the meal. Iron from FeSO(4) plus AA was more rapidly absorbed, resulting in a 35% greater relative AUC during the first 2 h than for NaFeEDTA (P < 0.001). Median (95% CI) fractional iron absorption from the FeSO(4)- and NaFeEDTA-fortified meals was 15.2% (11.0-19.5) and 6.0% (5.0-9.2), respectively (P < 0.001). In response to the FeSO(4)-fortified meal, there was an ~60% increase in median serum hepcidin (P < 0.05) but no significant change in NTBI. There was no significant change in serum hepcidin or NTBI after the NaFeEDTA-fortified meal. SIAC are a useful new tool to compare iron absorption profiles from different iron compounds in fortified foods. Even with the use of a very well absorbed ferrous iron compound, iron fortification in this population does not increase NTBI, suggesting a low risk for adverse health consequences.
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Preoperative haematinics and transfusion protocol reduce the need for transfusion after total knee replacement.
Cuenca, J, García-Erce, JA, Martínez, F, Cardona, R, Pérez-Serrano, L, Muñoz, M
International journal of surgery (London, England). 2007;(2):89-94
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Abstract
BACKGROUND Unilateral total knee replacement (TKR) can result in a substantial blood loss and 30-50% of these patients receive allogeneic blood transfusion (ABT), this transfusion rate may be even higher among anaemic patients. PATIENTS AND METHODS We assessed the requirements for ABT in 156 consecutive patients undergoing surgery for primary TKR, who received iron ferrous sulphate (256 mg/day; 80 mg of Fe(2+)), vitamin C (1000 mg/day) and folic acid (5mg/day) during the 30-45 days preceding surgery, and who were transfused if Hb <80 g/L and/or clinical signs/symptoms of acute anaemia/hypoxemia (Group 2). A previous series of 156 TKR patients serves as a control group (Group 1). RESULTS Compared to those in Group 1, patients in Group 2 presented a lower transfusion rate (5.8% vs. 32%, for Group 2 and Group 1, respectively; p<0.01), and a lower transfusion index (1.78+/-0.44 vs. 2.22+/-0.65 units per transfused patient, respectively; p<0.05). After patient's stratification according to a preoperative Hb above or below 130 g/L, the differences in transfusion rate remained significant, although 19% of patients from Group 2 still needed ABT if their preoperative Hb <130 g/L. CONCLUSION This protocol seems to be effective for avoiding ABT in non-anaemic TKR patients, whereas for anaemic patients another blood saving strategy, such us preoperative erythropoietin administration or postoperative blood salvage, should be added to further increase its effectiveness.
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Reversal of iron deficiency anemia-induced peripheral neuropathy by iron treatment in children with iron deficiency anemia.
Kabakus, N, Ayar, A, Yoldas, TK, Ulvi, H, Dogan, Y, Yilmaz, B, Kilic, N
Journal of tropical pediatrics. 2002;(4):204-9
Abstract
The effects of iron deficiency anemia (IDA) on nerve conduction and efficiency of iron therapy were investigated by peripheral nerve-electrophysiological measurements. Eighteen children (10 boys, eight girls; mean age 31 +/- 1.3 months) with IDA and 12 healthy children (six boys, six girls; mean age 29 +/- 1.3 months) were enrolled into the study. Nerve conduction velocity was measured in the median and posterior tibial nerve. After nerve conduction values were determined in the patients and controls, 6 mg/kg/24 h ferrous sulphate was given orally to the patients for 3 months and nerve conduction velocity tests were performed again. Median/motor and sensory nerve conduction velocity and tibial/motor nerve distal-amplitute values of children with IDA were lower than for the control group (p < 0.05, p < 0.01 and p < 0.001 respectively). With iron supplementation these values increased to the normal levels and even higher than control levels for some parameters. In correlation studies between whole blood parameters and nerve conduction velocity results, there was a correlation between median/sensory nerve conduction velocity values and serum iron levels. Additionally there was a correlation between some nerve conduction velocity values and age. In conclusion, the evidence from this preliminary study suggests that peripheral neuropathy may develop in children with IDA. Peripheral neuropathy symptoms in these patients may be improved by iron therapy.