Iron-chelating and anti-lipid peroxidation properties of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) in long-term iron loading β-thalassemic mice

Kulprachakarn, Kanokwan; Chansiw, Nittaya; Pangjit, Kanjana; Phisalaphong, Chada; Fucharoen, Suthat; Hider, Robert C.; Santitherakul, Sineenart; Srichairatanakool, Somdet

doi:10.12980/apjtb.4.2014apjtb-2014-0155

Cited by 7 publications

(3 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HEPC (ng/ml) and Ferritin (ng/ml) were estimated according to instructions of the manufacturer using ELISA. NTBI ( μ mol/L) that represents iron not bound to transferrin and not corresponding to heme and ferritin iron was estimated according to method described by [18] using HPLC technique.…”

Section: Methodsmentioning

confidence: 99%

Ameliorating Iron Overload in Intestinal Tissue of Adult Male Rats: Quercetin vs Deferoxamine

El-Sheikh

Ameen

AbdEl-Fatah

2018

Journal of Toxicology

View full text Add to dashboard Cite

Objective The aim of our study is to compare the role of the new natural alternative (Quercetin) with the current iron-chelation therapy (Deferoxamine (DFO)) in the effect of iron overload on small intestinal tissues and to investigate the possible underlying molecular mechanisms of such toxicity. Methods Forty-two adult male albino rats were divided into six groups: control groups, DFO, Quercetin, iron overload, iron overload+DFO, and iron overload+Quercetin groups. Animals received daily intraperitoneal injection of Deferoxamine (125 mg /kg), Quercetin (10 mg/kg), and ferric dextran (200 mg/kg) for 2 weeks. Results Iron overloaded group showed significant increase in serum iron, total iron binding capacity (TIBC), transferrin saturation percentage (TS %) hepcidin (HEPC), serum ferritin, nontransferrin bound iron (NTBI), and small intestinal tissues iron levels. Iron overload significantly increased the serum oxidative stress indicator (MDA) and reduced serum total antioxidant capacity (TAC). On the other hand, iron overload increased IL6 and reduced IL10 in small intestinal tissues reflecting inflammatory condition and increased caspase 3 reactivity indicating apoptosis and increased iNOs expressing cell indicting oxidative stress especially in ileum. In addition, it induced small intestinal tissues pathological alterations. The treatment with Quercetin showed nonsignificant differences as compared to treatment with DFO that chelated the serum and tissue iron and improved the oxidative stress and reduced tissue IL6 and increased IL10 and decreased caspase 3 and iNOs expressing cells in small intestinal tissues. Moreover, it ameliorated the iron overload induced pathological alterations. Conclusion Our study showed the potential role of Quercetin as iron chelator like DFO in case of iron overload induced small intestinal toxicity in adult rats because of its serum and tissue iron chelation, improvement of serum, and small intestinal oxidative stress, ameliorating iron induced intestinal inflammation, apoptosis, and histopathological alterations.

show abstract

Section: Methodsmentioning

confidence: 99%

Ameliorating Iron Overload in Intestinal Tissue of Adult Male Rats: Quercetin vs Deferoxamine

El-Sheikh

Ameen

AbdEl-Fatah

2018

Journal of Toxicology

View full text Add to dashboard Cite

show abstract

“…Normal vitamin D status was defined as serum 25‐OHD ≥30 ng/ml . Plasma NTBI concentration was quantified using the nitrilotriacetic acid chelation/high‐performance liquid chromatography method established by Singh et al LPI concentration was analyzed as previously described by Kulprachakarn et al Serum 25‐OHD, LPI, and NTBI levels were not measured in one patient due to inadequate specimen collection.…”

Section: Methodsmentioning

confidence: 99%

Prevalence of low bone mass among adolescents with nontransfusion‐dependent hemoglobin E/β‐thalassemia and its relationship with anemia severity

Nakavachara

Petchkul

Jeerawongpanich

et al. 2017

Pediatric Blood & Cancer

Self Cite

View full text Add to dashboard Cite

Background: Low bone mass is common among adolescents with transfusion-dependent -thalassemia despite adequate transfusion and iron chelation. However, there are few reports regarding bone mineral density (BMD) among adolescents with nontransfusion-dependent thalassemia (NTDT). Indeed, only BMD data in patients with nontransfusion-dependent (NTD) -thalassemia intermedia have been reported. No previous study has investigated BMD among adolescents with NTD hemoglobin (Hb) E/ -thalassemia. Objective:To determine the prevalence of low bone mass among adolescents with NTD Hb E/ -thalassemia and factors relating to low bone mass. Methods:We investigated BMD of lumbar spine (L2-L4; BMDLS) and total body (BMDTB), as measured by dual-energy X-ray absorptiometry, in 22 adolescents (aged 13.2-20 years) with NTD Hb E/ -thalassemia.Results: Low bone mass was found to be 18.2% and 22.7% at the lumbar spine (BMDLS Z-score adjusted for bone age and height age) and 13.6% and 9.1% at the total body (BMDTB Z-score adjusted for bone age and height age). Patients with mean Hb level <8 g/dl were more likely to have low bone mass (BMDLS and BMDTB Z-scores adjusted for bone age) compared to those with Hb level ≥ 8 g/dl. Mean Hb level correlated with BMDLS and BMDTB Z-scores adjusted for bone age. Conclusion:We demonstrated that a low Hb level was associated with low bone mass among adolescents with NTD Hb E/ -thalassemia. A significant proportion of low bone mass among these patients highlights the importance of appropriate management, including red cell transfusion, vitamin D and calcium supplementation for improved long-term bone health. K E Y W O R D Sadolescents, bone mineral density, Hb E/ -thalassemia, nontransfusion-dependent thalassemia (NTDT), thalassemia Abbreviations: BMD, bone mineral density; BMDLS, BMD of lumbar spine (L2-L4); BMDTB, BMD of total body; DXA, dual-energy X-ray absorptiometry; Hb, hemoglobin; LIC, liver iron concentration; LPI, labile plasma iron; NTBI, nontransferrin-bound iron; NTD, nontransfusion-dependent; NTDT, non-transfusion-dependent thalassemia; TDT, transfusion-dependent thalassemia; 25-OHD, 25-hydroxyvitamin D

show abstract

“…Chemically synthesized iron chelators have been proposed for the treatment of many diseases associated with iron overload (Pangjit et al, 2015, Kulprachakarn et al, 2014, Chansiw et al, 2014). However, more adverse effects were represented during the treatment schedules that made many pharmacologists to devote their efforts to study new treatment strategies based on naturally occurred iron chelators of plant origin.…”

Section: Introductionmentioning

confidence: 99%

Green tea activity and iron overload induced molecular fibrogenesis of rat liver

Albasher

2019

Saudi Journal of Biological Sciences

View full text Add to dashboard Cite

Iron overload toxicity was shown to associate with chronic liver diseases which lead to hepatic fibrosis and subsequently the progression to cancer through oxidative stress and apoptotic pathways. Green tea potential activity as chelating, anti-oxidative, or anti-apoptotic mechanisms against metal toxicity was poorly clarified. Here, we are trying to evaluate the anti-oxidant and anti-apoptotic properties of green tea in the regulation of serum hepcidin levels, reduction in iron overloads, and improve of liver fibrosis in iron overloaded experimental rats. Three groups of male adult rats were randomly classified into three groups and treated as follows: control rats, iron treated rats for two months in drinking water followed by either vehicle or green tea extract (AGTE; 100 mg/kg) treatment for 2 more months. Thereafter, we studied the effects of AGTE on iron overload-induced lipid peroxidation, anti-oxidant depletion, liver cell injury and apoptosis. Treatment of iron-overloaded rats with AGTE resulted in marked decreases in iron accumulation within liver, depletion in serum ferritin, and hepcidin levels. Iron-overloaded rats had significant increase in malonyldialdehyde (MDA), a marker of lipid peroxidation and nitric oxide (NO) in liver when compared to control group. Also, significant change in cytochrome c and DNA content as apoptotic markers were reported in iron treated rats. The effects of iron overload on lipid peroxidation, NO levels, cytochrome c and DNA content were significantly reduced by the intervention treatment with AGTE (P < 0.001). Furthermore, the endogenous anti-oxidant capacities/levels (TAC) in liver were also significantly decreased in chronic iron overload and administration of AGTE restored the decrease in the hepatic antioxidant activities/levels. Also, hepatic hepcidin was shown to be significantly correlated with oxidative and apoptotic relating biomarkers as well as an improvement in liver fibrosis of iron treated rats following AGTE treatment. In-vitro analysis showed that, the improvement in iron toxicity of the liver depend mainly on antioxidant and protective ability of green tea polyphenolic compounds especiallyepigallocatechin-3-gallate (EGCG). Our study showed that green tea extract (GTE) ameliorates iron overload induced hepatotoxicity, apoptosis and oxidative stress in rat liver via inhibition of hepatic iron accumulation; improve of liver antioxidant capacity, and down regulation of serum hepcidin as well as reduction in the release of apoptotic relating proteins.

show abstract

Iron-chelating and anti-lipid peroxidation properties of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) in long-term iron loading β-thalassemic mice

Abstract: CM1 could be an effective oral iron chelator that can reduce iron overload and lipid peroxidation in chronic iron overload β-thalassemic mice.

Cited by 7 publications

References 39 publications

Ameliorating Iron Overload in Intestinal Tissue of Adult Male Rats: Quercetin vs Deferoxamine

Ameliorating Iron Overload in Intestinal Tissue of Adult Male Rats: Quercetin vs Deferoxamine

Prevalence of low bone mass among adolescents with nontransfusion‐dependent hemoglobin E/β‐thalassemia and its relationship with anemia severity

Green tea activity and iron overload induced molecular fibrogenesis of rat liver

Contact Info

Product

Resources

About