Combined treatment of 3-hydroxypyridine-4-one derivatives and green tea extract to induce hepcidin expression in iron-overloaded β-thalassemic mice

Upanan, Supranee; Pangjit, Kanjana; Uthaipibull, Chairat; Fucharoen, Suthat; McKie, Andrew T.; Srichairatanakool, Somdet

doi:10.1016/j.apjtb.2015.09.007

Cited by 13 publications

(15 citation statements)

References 50 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In accordance with previous studies (Jamsai et al, 2005;Nai et al, 2012;Upanan et al, 2015), we observed thalassemia intermedia phenotype in BKO mice during adolescence and adulthood as characterized by microcytic anemia, extramedullary hematopoiesis as well as iron accumulation in the liver and spleen. In the present study, hematological results revealed relatively lower red blood cell count and hemoglobin levels in both WT Table 3 Iron deposition score in the liver, spleen and duodenum of male wild type and thalassemic mice at the age of 6-7 weeks and 16-20 weeks.…”

Section: Discussionsupporting

confidence: 92%

Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood

Sanyear

Butthep

Eamsaard

et al. 2020

PeerJ

Self Cite

View full text Add to dashboard Cite

Background: Iron overload is one of common complications of β-thalassemia. Systemic iron homeostasis is regulated by iron-regulatory hormone, hepcidin, which inhibits intestinal iron absorption and iron recycling by reticuloendothelial system. In addition, body iron status and requirement can be altered with age. In adolescence, iron requirement is increased due to blood volume expansion and growth spurt. Heterozygous β-globin knockout mice (Hbb th3/+ ; BKO) is a mouse model of thalassemia widely used to study iron homeostasis under this pathological condition. However, effects of age on iron homeostasis, particularly the expression of genes involved in hemoglobin metabolism as well as erythroid regulators in the spleen, during adolescence have not been explored in this mouse model. Methods: Iron parameters as well as the mRNA expression of hepcidin and genes involved in iron transport and metabolism in wildtype (WT) and BKO mice during adolescence (6-7 weeks old) and adulthood (16-20 weeks old) were analyzed and compared by 2-way ANOVA. Results: The transition of adolescence to adulthood was associated with reductions in duodenal iron transporter mRNA expression and serum iron levels of both WT and BKO mice. Erythrocyte parameters in BKO mice remained abnormal in both age groups despite persistent induction of genes involved in hemoglobin metabolism in the spleen and progressively increased extramedullary erythropiesis. In BKO mice, adulthood was associated with increased liver hepcidin and ferroportin mRNA expression along with splenic erythroferrone mRNA suppression compared to adolescence. Conclusion: Our results demonstrate that iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood. The present study underscores the importance of the age of thalassemic mice in the study of molecular or pathophysiological changes under thalassemic condition.Abboud S, Haile DJ. 2000. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. AB, Paw BH. 2011. Identification of distal cis-regulatory elements at mouse mitoferrin loci using zebrafish transgenesis. Molecular and Cellular Biology 31 (7):

show abstract

Section: Discussionsupporting

confidence: 92%

Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood

Sanyear

Butthep

Eamsaard

et al. 2020

PeerJ

Self Cite

View full text Add to dashboard Cite

show abstract

“…Thus, rats of control group supplemented only tap water, whereas iron overloaded and AGTE groups provided with drinking water containing 3 mg/L of Fe 2+ (using 8.3 mg/L of FeSO 4 ). The dose of AGTE was selected based on previous studies (Upanan et al, 2015, Kim et al, 2009). In most animal studies, a dose range of 50–200 mg/kg body weight AGTE exhibited a good anti-inflammatory and anti-fibrotic activity and seemed to have no adverse effects on human (Saewong et al, 2010, Kim et al, 2009, Ibrahim et al, 2015).…”

Section: Methodsmentioning

confidence: 99%

“…A microwave cabinet was used for drying freshly harvested green tea leaves (Camellia sinensis) (Upanan et al, 2015). To prepare green tea extract, hot water is used.…”

Section: Methodsmentioning

confidence: 99%

“…In iron overloaded experimental models, hepcidin levels were regulated with both drug therapy and naturally occurred iron chelators (Porter et al, 2014, Gu et al, 2013;). Although, little is known about the exact regulation mechanisms proposed under these conditions, only green tea alone or in combination with other drugs chelating toxic iron in plasma and tissues, and increasing the levels of hepcidin expression (Kautz et al, 2014, Yun and Vincelette, 2015, Upanan et al, 2015). From the previous data, our hypothesis that green tea as naturally occurred iron chelator of plant origin could ameliorates iron overload toxicity and prevent most iron related diseases especially liver diseases.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

“…1). 31 Our GTE contained 29.0 mg of EGC, 90.75 mg of ECG, and 24.75 mg of EGCG (a total of 144.5 mg catechins) per gram dry weight and used in this study.…”

Section: Gte Preparation and Analysismentioning

confidence: 99%

Decrement in Cellular Iron and Reactive Oxygen Species, and Improvement of Insulin Secretion in a Pancreatic Cell Line Using Green Tea Extract

Koonyosying¹,

Uthaipibull

Fucharoen

et al. 2019

Pancreas

Self Cite

View full text Add to dashboard Cite

show abstract

Combined treatment of 3-hydroxypyridine-4-one derivatives and green tea extract to induce hepcidin expression in iron-overloaded β-thalassemic mice

Cited by 13 publications

References 50 publications

Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood

Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood

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

Decrement in Cellular Iron and Reactive Oxygen Species, and Improvement of Insulin Secretion in a Pancreatic Cell Line Using Green Tea Extract

Contact Info

Product

Resources

About