• The Journal of Internal Korean Medicine
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• v.44 no.2
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• pp.252-259
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• 2023

Objectives: This study identified the effect of Korean medicine treatment on a patient with iron overload who discontinued iron chelation therapy. Methods: A 64-year-old woman with iron overload was treated with Saenggangunbi-tang from November 14, 2022, to March 15, 2023, to reduce fatigue and improve laboratory findings. We observed changes in the symptoms and improvement of laboratory findings during the four-month treatment. Results: The approximately four-month treatment with Saenggangunbi-tang showed considerable improvement in laboratory findings and fatigue. In addition, no adverse effects, such as liver injury, were observed during Korean medicine treatment. Conclusion: This study suggests the availability of Saenggangunbi-tang as a therapeutic option for managing patients with iron overload.

• Animal cells and systems
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• v.13 no.2
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• pp.105-112
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• 2009

In this study, the effects of iron on cytochrome c oxidase (CcO) in rat lung mitochondria were examined. Similar to liver mitochondria, iron accumulated considerably in lung mitochondria (more than 2-fold). Likewise, the reactive oxygen species and nitric oxide (NO) content of mitochondria were increased by more than 50% and 100%, respectively. NO might be produced by nitric oxide synthase (NOS), eNOS and iNOS type, with particular contribution by NOS in mitochondria. The respiratory control ratio of iron overloaded lung mitochondria dropped to nearly 50% due to increased state 4. Likewise, cytochrome c oxidase activity was lowered significantly to approximately 50% due to excess iron. Real-time PCR revealed that the expression of isoforms 1 and 2 of subunit IV of CeO was enhanced greatly under excess iron conditions. Taken together, these results show that oxidative phosphorylation within lung mitochondria may be influenced by iron overload through changes in cytochrome c oxidase and NO.

• Proceedings of the Korean Society of Food Hygiene and Safety Conference
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• 2002.05a
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• pp.138-138
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• 2002

Oxidative stress has been associated with a number of diseases in human. Among the sources that can generate oxidative stress, it has been reported that iron can generate reactive oxygen species (ROS)with thiol. In iron overload state, increased thiol levels in plasma appeared to be associated with human mortality. In this study we examined whether iron could interact with thiols in plasma, generating ROS. In human plasma, unlike with Fe(III), Fe(II) increased lucigenin-enhanced chemiluminescence in concentration-dependent manner, and this was inhibited by SOD. Boiling of plasma did not affect chemiluminescence induced by Fe(II). Hovever, thiol depletion in plasma by pretreatment with N-ethylmaleimide (NEM)decreased Fe(II)-induced chemiluminescence significantly, suggesting that Fe(II) generated superoxide anion by the nonenzymatic reaction with plasma thiol. Consistent with this findings, albumin, the major thiol contributor in plasma, also generated ROS with Fe(II) and this generation was inhibited by pretreatment with NEM. Treatment with Fe(II) to plasma resulted un significant reduction of oxygen radical absorbance capacity (ORAC) value, suggest that total antioxidant capacity could diminished in iron overload state. In conclusion, In iron overload state, plasma may be affected by oxidative stress mediated by nonenzymatic reaction of Fe (II)with plasma thiol.

• BLOOD RESEARCH
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• v.53 no.4
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• pp.314-319
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• 2018

Background Iron overload is a risk factor affecting all patients with thalassemia intermedia (TI). We aimed to determine whether there is a relationship of serum ferritin (SF) and alanine aminotransferase (ALT) with liver iron concentration (LIC) determined by R2 magnetic resonance imaging (R2-MRI), to estimate the most relevant degree of iron overload and best time to chelate in patients with TI. Methods In this cross-sectional study, 119 patients with TI (mean age years) were randomly selected and compared with 120 patients who had a diagnosis of thalassemia major (TM). Correlations of LIC, as determined by R2-MRI, with SF and ALT levels, were assessed in all participants. A P-value <0.05 was considered statistically significant. Results SF and LIC levels were lower in patients with TI than in those with TM; only ferritin values were significant. We found a statistically significant relationship between SF and LIC, with cut-off estimates of SF in patients with TI who had splenectomy and those who entered puberty spontaneously (916 and 940 ng/mL, respectively) with LIC >5 mg Fe/g dry weight (P<0.0001). A significant relationship was also found for patients with TI who had elevated ALT level (63.5 U/L), of 3.15 times the upper normal laboratory limit, using a cut-off for LIC ${\geq}5mg\;Fe/g\;dry\;weight$. Conclusion We determined the cut-off values for ALT and SF indicating the best time to start iron chelation therapy in patients with TI, and found significant correlations among iron overload, SF, and ALT.

• The Korean Journal of Blood Transfusion
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• v.29 no.3
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• pp.273-281
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• 2018

Background: Ferritin is used to detect iron overload in patients with chronic red blood cell transfusions. Although ferritin reflects the amount of iron storage in the body, it may increase nonspecifically in inflammation and infection. This study analyzed the cause of increased ferritin and the association with a red blood cell (RBC) transfusion. Methods: The medical records of patients who visited the authors' hospital from January to December 2017 and underwent a ferritin test were reviewed retrospectively. Hyperferritinemia was defined as a ferritin level more than 1,000 ng/mL. The causes of hyperferritinemia were investigated by examining the laboratory findings and medical records. Results: The results revealed 417 cases of hyperferritinemia in 238 patients during the period. The most common diseases were hematologic malignancies from 125 cases (30.0%) in 31 patients and infectious diseases were the second most common. Iron overload was suspected in 119 cases in 33 patients, and 12 patients (76 cases) were transfused with more than 8 units of RBC for 1 year before the test. Conclusion: In hyperferritinemia, the rate of iron overload is high considering the underlying diseases and chronic RBC transfusion. To determine iron storage status accurately, it will be helpful to measure the C-reactive protein (CRP) and iron saturation in the ferritin test. Careful attention should be paid to habitual iron formulations and frequent transfusions due to the possibility of iron overload.

• Animal cells and systems
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• v.8 no.2
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• pp.97-103
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• 2004

The cytotoxic effect of iron was examined in peritoneal macrophage to determine contributing factors by iron injection to rat. Viability was reduced by 24% by the iron-overload and by 30% by short-term iron addition. Total iron was increased by 45% in the iron-overloaded with remarkable elevation (9 to 14 fold) in the presence of $FeSO_4$. Free calcium was also increased by 19% in control and 44% in iron-overloaded group due to additional $FeSO_4$ NO and MDA were increased by 40% and 136%, respectively, with significant reduction (37%) of NAD(P)H. RCR and cytochrome c oxidase activity were lowered approximately by 10% with reduction of mitochondrial membrane potential. Addition of iron was frequently associated with altered distribution of mitochondria of high membrane potential in the iron-overloaded macrophage. These results suggest altered mitochondria with high NO and low NAD(P)H due to iron.

• Animal cells and systems
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• v.14 no.2
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• pp.91-98
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• 2010

Male rats were given a single injection of iron, and temporal changes in iron content and iron-induced effects were examined in heart cellular fractions. Over a period of 72 h, the contents of total and labile iron, reactive oxygen species, and NO in tissue homogenate, nuclear debris, and postmitochondrial fractions were mostly constant, but in mitochondria they continuously increased. An abrupt decrease in membrane potential and NAD(P)H at 12 h was also found in mitochondria. The respiratory control ratio was reduced slowly with a slight recovery at 72 h, suggesting uncoupling by iron.While the ATP content of tissue homogenate decreased steadily until 72 h, it showed a prominent increase in mitochondria at 12 h. Total iron and calcium concentration also progressively increased in mitochondria over 72 h. Enzyme activity of the oxidative phosphorylation system was significantly altered by iron injection: activities of complexes I, III, and IV were reduced considerably, but complex II activity and the ATPase activity of complex V were enhanced. A reversal of activity in complexes I and II at 12 h suggested reverse electron transfer due to iron overload. These results support the argument that mitochondrial activities including oxidative phosphorylation are modulated by excessive iron.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.2
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• pp.307-313
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• 2001

Iron excess is known to affect long-term iron accumulation and tissue change such as fibrosis in liver. To determine the changes of expression level of genes associated with fibrosis by short-term iron exposure, we measured liver mRNA levels by reverse transcription polymerase chain reaction (RT-PCR) in rats fed dietary carbonyl iron (3%, wt/wt) for 9 weeks. The results showed that the expression of the collagen (I, III) and transforming growth factor (TGF)-$\beta$I mRNAs was enhanced in high-dose iron treated rat, compared to normal-dose iron treated rat. An electron microscopy study revealed that excess iron caused increase of collagen fibrils in liver. The cell shapes and compositions of hepatocytes and extracellular matrix(ECM) in liver were changed by the iron-treatment. Also, necrosised hepatocytes were broadly seen in ECM. Taken together, we suggest that iron overload affects changes of collagen and TGF-$\beta$I gene expression and these changes are associated with liver fibrogenesis.

• Journal of Microbiology and Biotechnology
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• v.14 no.3
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• pp.470-473
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• 2004

In the yeast Saccharomyces cerevisiae, iron can be toxic. Because of this phenomenon, its metabolism of iron is strictly regulated. We have constructed a model system in which cell growth is defected during periods of iron over-load. When $Aft1-1^{up}$ protein was overexpressed with Ga110 promoter, a galactose inducible promoter, cell growth was defected and levels of CLN2 transcript decreased. However transcript levels of AFT1 and FET3 genes increased over time in a consistent manner throughout the course of $AFT1-1^{up}$ overexpression. We have screened to find genes to suppress cell growth defect by iron overload with YEp-derived high copy yeast genomic DNA library and found that high copy of Rmelp suppressed cell growth defects. Rme1p has been known as an activator protein of CLN2 gene expression. Taking these results together, we suggest that the yeast cell cycle is arrested at the $G_1$, phase by iron overload via Cln2p.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.27 no.4
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• pp.215-223
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• 2024

Purpose: Patients who receive frequent blood transfusions are at an elevated risk of developing hepatic fibrosis due to iron overload in the liver. In this study, we evaluated the effectiveness of transient elastography (TE) (FibroScan^®) for assessing liver fibrosis in patients with pediatric cancer. Methods: We enrolled 106 consecutive cases of acute leukemia in individuals under 21 years of age. The participants were followed for 2 years. Based on their serum ferritin (SF) levels, the patients were divided into two groups: group 1 (SF≥300 ng/mL) and group 2 (SF<300 ng/mL). A liver FibroScan^® was performed, and a p-value of less than 0.05 was considered statistically significant. Results: Among the various parameters in the liver function test (LFT), alkaline phosphatase was significantly higher in a subgroup of patients aged 5-8 years in group 2 compared to those in group 1. The indices of liver fibrosis determined by TE, including the FibroScan score, controlled attenuation parameter score, steatosis percentage, and meta-analysis of histological data in viral hepatitis score, as well as indirect serum markers of liver fibrosis such as the aminotransferase (AST)/alanine aminotransferase (ALT) ratio, Fibrosis 4 score, and AST to platelet ratio index, did not differ significantly between the two groups. The association between the TE results and LFT parameters was only significant for ALT. Conclusion: Transfusion-associated iron overload does not have a significant correlation with severe liver fibrosis. FibroScan^® is not a sensitive tool for detecting early stages of fibrosis in survivors of pediatric leukemia.