scholarly journals Are Mangiferin and Mangiferin-Containing Plant Extracts Helpful for Iron-Loaded Transfusion-Dependent and Non-Transfusion-Dependent Thalassaemia Patients?

2018 ◽  
Vol 11 (1) ◽  
pp. 29-43 ◽  
Author(s):  
Ari Estuningtyas ◽  
Klaus Zwicker ◽  
Tri Wahyuni ◽  
Purnama Fajri ◽  
Pustika Amalia Wahidiyat ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Complex ◽  
Blood Levels ◽  
Plasma Iron ◽  
Gastric Tubes ◽  
Oral Doses ◽  
Great Burden ◽  
Iron Excretion

Treatment of iron overload in thalassaemia is still a great burden for patients, their families and the health care system in developing countries like Indonesia, because of expensiveness and unwanted side effects of chemical iron-chelating therapeutics. This animal study investigates an extract from the leaves of Mangifera foedica L (EMF) and its major active compound, mangiferin, for chelating and antioxidant treatment of iron overload. Sixty rats were randomly divided into 10 groups: control, iron overload (IO), and IO with mangiferin doses between 50 and 200 mg/g BW or 2390 mg of EMF, applied via gastric tubes. For comparison, deferiprone (DFP) was used. Iron overload was induced by intraperitoneal iron dextran resembling two models, transfusion-dependent (TDT) or nontransfusion-dependent thalassaemia (NTDT). Increasing oral doses of mangiferin and EMF did not result in higher mangiferin plasma levels; however, mangiferin administered for four weeks roughly doubled blood levels compared to two weeks. In the TDT model, mangiferin significantly lowered ferritin levels by 21% and plasma iron levels by 60% (EMF by 50%), almost like DFP (by 70%) and increased iron excretion 6-fold via urine (DFP 15-fold, EMF 2-fold). In the NTDT model mangiferin and EMF decreased ferritin levels significantly by about 30%, without significantly decreasing excess plasma iron. Mangiferin increased iron excretion via urine 4-fold (EMF 2-fold) and tended to diminish Fe accumulation in liver and heart. Iron chelating effects of EMF were weaker than of mangiferin, but its in vivo antioxidant activity was stronger. In vitro, both mangiferin and the mangiferin/FeIII complex are potent superoxide radical scavengers, the iron complex being superior.

scholarly journals Labile plasma iron in iron overload: redox activity and susceptibility to chelation

Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2670-2677 ◽  
Author(s):  
Breno P. Esposito ◽  
William Breuer ◽  
Pornpan Sirankapracha ◽  
Pensri Pootrakul ◽  
Chaim Hershko ◽  
...  
Keyword(s):  
Iron Overload ◽  
Oral Treatment ◽  
Oxidation Products ◽  
Redox Activity ◽  
Iron Chelators ◽  
Plasma Iron ◽  
Redox Active ◽  
Reactive Radicals

Abstract Plasma non-transferrin-bound-iron (NTBI) is believed to be responsible for catalyzing the formation of reactive radicals in the circulation of iron overloaded subjects, resulting in accumulation of oxidation products. We assessed the redox active component of NTBI in the plasma of healthy and β-thalassemic patients. The labile plasma iron (LPI) was determined with the fluorogenic dihydrorhodamine 123 by monitoring the generation of reactive radicals prompted by ascorbate but blocked by iron chelators. The assay was LPI specific since it was generated by physiologic concentrations of ascorbate, involved no sample manipulation, and was blocked by iron chelators that bind iron selectively. LPI, essentially absent from sera of healthy individuals, was present in those of β-thalassemia patients at levels (1-16 μM) that correlated significantly with those of NTBI measured as mobilizer-dependent chelatable iron or desferrioxamine chelatable iron. Oral treatment of patients with deferiprone (L1) raised plasma NTBI due to iron mobilization but did not lead to LPI appearance, indicating that L1-chelated iron in plasma was not redox active. Moreover, oral L1 treatment eliminated LPI in patients. The approach enabled the assessment of LPI susceptibility to in vivo or in vitro chelation and the potential of LPI to cause tissue damage, as found in iron overload conditions. (Blood. 2003;102:2670-2677)

scholarly journals The preventive effect of Mangifera foetida L. leaf extract administered simultaneously to excess iron on markers of iron overload in Spraque-Dawley rats

2018 ◽  
Vol 26 (4) ◽  
pp. 246-52
Author(s):  
Purnama Fajri ◽  
Ari Estuningtyas ◽  
Melva Louisa ◽  
Hans-Joachim Freisleben
Keyword(s):  
Iron Overload ◽  
Leaf Extract ◽  
Blood Levels ◽  
Sprague Dawley ◽  
Leaf Extracts ◽  
In Vivo Models ◽  
Excess Iron ◽  
Before And After

Background: Recently, there is no agent available for the prevention of iron overload (IO) in thalassemia patients. Previous studies showed that Mangifera foetida L. leaf extracts reduced the levels of iron in IO in vitro and in vivo models. The present study aimed to determine the efficacy of Mangifera foetida L. leaf extract in the prevention of IO induced in rats.Methods: Thirty male Sprague-Dawley rats were divided into 5 groups: control (untreated), IO, 3 treatment groups with leaf extract equivalent to 50, 100, and 200 mg of mangiferin per kg BW. Fe-dextran (15 mg) was administered intraperitoneally twice a week for 4 weeks to all groups except control (IO, DSM50, DSM100, and DSM200). Urine and blood samples were taken before and after treatments. After 4 weeks of treatment, rats were terminated, and samples of spleen, liver, and heart were taken. Ferritin and mangiferin levels and SOD activities were determined in plasma. Iron levels were measured in plasma, urine, and spleen.Results: Experimental IO increased plasma Fe content 4.23 times and plasma ferritin levels 6.9 times vs normal. Mangifera foetida L. leaf extract DSM50 resulted in the highest blood levels of 212 ng mangiferin per mL and moderately, although not significant, prevented increased plasma ferritin levels and IO in organs and protected against oxidative stress.Conclusion: Aqueous Mangifera foetida L. leaf extract may be useful to prevent IO and oxidative stress in thalassemia patients.

Effects of Heparin Oligosaccharides with High Affinity for Antithrombin III in Experimental Venous Thrombosis

1982 ◽  
Vol 47 (03) ◽  
pp. 244-248 ◽  
Author(s):  
D P Thomas ◽  
Rosemary E Merton ◽  
T W Barrowcliffe ◽  
L Thunberg ◽  
U Lindahl
Keyword(s):  
Antithrombin Iii ◽  
Specific Activity ◽  
High Specific Activity ◽  
Factor Xa ◽  
Blood Levels ◽  
Thrombin Time ◽  
High Affinity ◽  
Very High

SummaryThe in vitro and in vivo characteristics of two oligosaccharide heparin fragments have been compared to those of unfractionated mucosal heparin. A decasaccharide fragment had essentially no activity by APTT or calcium thrombin time assays in vitro, but possessed very high specific activity by anti-Factor Xa assays. When injected into rabbits at doses of up to 80 ¼g/kg, this fragment was relatively ineffective in impairing stasis thrombosis despite producing high blood levels by anti-Xa assays. A 16-18 monosaccharide fragment had even higher specific activity (almost 2000 iu/mg) by chromogenic substrate anti-Xa assay, with minimal activity by APTT. When injected in vivo, this fragment gave low blood levels by APTT, very high anti-Xa levels, and was more effective in preventing thrombosis than the decasaccharide fragment. However, in comparison with unfractionated heparin, the 16-18 monosaccharide fragment was only partially effective in preventing thrombosis, despite producing much higher blood levels by anti-Xa assays.It is concluded that the high-affinity binding of a heparin fragment to antithrombin III does not by itself impair venous thrombogenesis, and that the anti-Factor Xa activity of heparin is only a partial expression of its therapeutic potential.

scholarly journals The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 186
Author(s):  
Maria Natalia Calienni ◽  
Daniela Maza Vega ◽  
C. Facundo Temprana ◽  
María Cecilia Izquierdo ◽  
David E. Ybarra ◽  
...  
Keyword(s):  
Side Effects ◽  
Water Solubility ◽  
Polymeric Micelles ◽  
Skin Penetration ◽  
Distribution Volume ◽  
And Performance ◽  
Oral Doses ◽  
Advanced Basal Cell Carcinoma

Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems were the most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformable liposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can be loaded in several delivery systems for topical application. These findings may be also useful for the consideration of topical delivery of other drugs with a low water solubility.

scholarly journals Pharmacokinetics of EDP-420 after Multiple Oral Doses in Healthy Adult Volunteers and in a Bioequivalence Study

2009 ◽  
Vol 53 (8) ◽  
pp. 3218-3225 ◽  
Author(s):  
Li-Juan Jiang ◽  
Yat Sun Or
Keyword(s):  
Systemic Exposure ◽  
Bioequivalence Study ◽  
Respiratory Pathogens ◽  
Capsule Formulation ◽  
Dose Study ◽  
Effect Of Food ◽  
Tract Infections ◽  
Oral Doses

ABSTRACT EDP-420 (also known as EP-013420, or S-013420) is a first-in-class bridged bicyclolide currently in clinical development for the treatment of respiratory tract infections (RTI) and has previously shown favorable pharmacokinetic (PK) and safety profiles after the administration of single oral doses of a suspension to healthy volunteers. Here we report its PK profile after the administration of multiple oral doses of a suspension to healthy adults. Bioequivalence between suspension and capsule formulations, as well as the effect of food, is also reported. The most important PK features of EDP-420 observed in these clinical studies are its long half-life of 17 to 18 h and its high systemic exposure, which support once-daily dosing and treatment durations potentially shorter than those of most other macrolide antibiotics. EDP-420 is readily absorbed following oral administration in both suspension and capsule formulations. In the multiple-oral-dose study, steady state was achieved on day 1 by using a loading dose of 400 mg/day, followed by 2 days of 200 mg/day. A high-fat meal had no effect on the bioavailability of EDP-420 administered in a capsule formulation. EDP-420 was well tolerated, with no serious or severe adverse events reported, and no subject was discontinued from the study due to an adverse event. Based on its human PK and safety profiles, together with its in vitro/in vivo activities against common respiratory pathogens, EDP-420 warrants further development, including trials for clinical efficacy in the treatment of RTI.

Selection of Hydroxypyridin-4-Ones for the Treatment of Iron Overload Using In Vitro and In Vivo Models

Hemoglobin ◽  
1988 ◽  
Vol 12 (5-6) ◽  
pp. 593-600 ◽  
Author(s):  
E. R. Huehns ◽  
J. B. Porter ◽  
R. C. Hider
Keyword(s):  
Iron Overload ◽  
In Vivo Models ◽  
Selection Of

IN VITRO DEMONSTRATION OF "HEPARIN REBOUND"

1987 ◽  
Author(s):  
C Taylor ◽  
R F Baugh
Keyword(s):  
Whole Blood ◽  
Cardiovascular Surgery ◽  
Anticoagulant Activity ◽  
Blood Levels ◽  
In Vitro Test ◽  
Neutralizing Activity ◽  
Vitro Test ◽  
The Stability

"Heparin rebound", the in vivo appearance of measurable heparin anticoagulant activity following theapparent neutralization of heparin by protamine, hasbeen a problem sporadically associated with the use of heparin in cardiovascular surgery. A number of mechanisms have been proposed to explain rebound, and to some extent each may contribute to the phenomena. As yet no reliable, predictable method has been demonstrated for measuring, reproducing or quantifying "heparin rebound".We have demonstrated and measured the appearance of heparin anticoagulant activity following neutralization with protamine in citrated whole blood. The reappearance of heparin anticoagulant activity was associated with a rapid loss of protamine. The loss of protamine followed 1st order enzyme kinetics, and was indicative of the action of an enzyme. The anticoagulant activity which eappeared could be titrated againwith protamine. The loss of protamine neutralizing activity, in whole blood, could be followed by titration with heparin using a recalcified activated clotting time. The rate of loss varied with both individual blood donors and with the type and source of protamine. The rate of loss of protamine was great enough to influence in. vivo heparin/protamine neutralization ratios, i.e. at 4 units of heparin/ml, 1 unit/ml anticoagulant activity was routinely recovered within 30 minutes following initial neutralization. The indications for cardiovascular surgery are:1)the in vivo neutralization ratio should be adjusted to account for loss of protamine activity, 2) the higherthe blood levels of heparin used during surgery, themore significant the potential for heparin rebound, and 3) protamines may be evaluated in an in vitro test which measures the stability of protamine neutralizing activity in whole blood.

scholarly journals Antischistosomal Activities of Mefloquine-Related Arylmethanols

2012 ◽  
Vol 56 (6) ◽  
pp. 3207-3215 ◽  
Author(s):  
Katrin Ingram ◽  
William Ellis ◽  
Jennifer Keiser
Keyword(s):  
Body Weight ◽  
Worm Burden ◽  
Structural Features ◽  
Content Type ◽  
Antischistosomal Activity ◽  
Oral Doses ◽  
Related Compounds ◽  
Insight Into

ABSTRACTInteresting antischistosomal properties have been documented for the antimalarial mefloquine, a 4-quinolinemethanol. We evaluated the antischistosomal activities of nine mefloquine-related compounds belonging to the 4-pyridinemethanols, 9-phenanthrenmethanols, and 4-quinolinemethanols. Eight compounds revealed high activities againstSchistosoma mansoni in vitro, with two drugs (the 4-quinolinemethanols WR7573 and WR7930) characterized by significantly lower half-maximal inhibitory concentrations (IC50s) (2.7 and 3.5 μM, respectively) compared to mefloquine (11.4 μM). Mefloquine and WR7930 showed significantly decreased IC50s when incubated in the presence of hemoglobin. High worm burden reductions (WBR) were obtained with enpiroline (WBR, 82.7%; dosage, 200 mg/kg of body weight) and itsthreoisomers (+)-threo(WBR, 100%) and (−)-threo(WBR, 89%) and with WR7930 (WBR, 87%; dosage, 100 mg/kg) against adultS. mansoniin mice. Furthermore, excellentin vitroandin vivoantischistosomal activity was observed for two WR7930-related structures (WR29252 and WR7524). In addition, mefloquine (WBR, 81%), enpiroline (WBR, 77%), and WR7930 (WBR, 100%) showed high activities againstS. haematobiumharbored in mice following single oral doses of 200 mg/kg. These results provide a deeper insight into the structural features of the arylmethanols that rule antischistosomal activity. Further studies should be launched with enpiroline and WR7930.

Efficacy of Different Hexacyanoferrates(II) in Inhibiting the Intestinal Absorption of Radiocaesium in Rats

1990 ◽  
Vol 45 (6) ◽  
pp. 676-680 ◽  
Author(s):  
Bernd Dresow ◽  
Peter Nielsen ◽  
Hellmuth C. Heinrich
Keyword(s):  
Side Effects ◽  
Binding Capacity ◽  
Domestic Animals ◽  
Inhibitory Effect ◽  
Time Interval ◽  
Oral Doses ◽  
Severe Nuclear Accident ◽  
Cobalt And Nickel

Abstract The inhibitory effect of various oral doses of different hexacyanoferrate(II) compounds (HCF) and the influence of the time interval of HCF-administration on intestinal 134Cs-absorption was studied in rats. Optimum inhibition was obtained by administration of HCF together with or 2 min before oral 134Cs loading. Using appropriate low amounts (0.1 -0.5 mg) of the different HCF compounds, the inhibitory effect increased in the sequence KZnHCF < KCuHCF < FeHCF < KCoHCF = KNiHCF < NH4FeHCF = KFeHCF . Oral administration of 5 mg (0.5 mg) of KFeHCF , together with 134CsCl loading, reduces 134Cs-absorption from 41 % (control) to 0.8% (2.8%). Zinc-, copper-, cobalt, and nickel hexacyanoferrates(II), despite showing a high caesium sorption capacity in vitro, were less effective in rats and are not suited for in vivo application, also because they may produce toxic side effects. As a consequence, the orally administered colloidal-soluble iron (III) hexacyanoferrates(II) (NH4Fe[Fe(CN)6] and KFe[Fe(CN)6]) have to be considered as the most valuable countermeasure against radiocaesium absorption for humans and domestic animals in the case of a severe nuclear accident in the future. Manganese oxide, a non-hexacyanoferrate(II) compound with known in vitro caesium binding capacity, showed no inhibitory effect on radiocaesium absorption in rats.

scholarly journals Trematocidal Activity of Praziquantel and Artemisinin Derivatives: In Vitro and In Vivo Investigations with Adult Echinostoma caproni

2006 ◽  
Vol 50 (2) ◽  
pp. 803-805 ◽  
Author(s):  
Jennifer Keiser ◽  
Reto Brun ◽  
Bernard Fried ◽  
Jürg Utzinger
Keyword(s):  
Body Weight ◽  
Worm Burden ◽  
Echinostoma Caproni ◽  
Artemisinin Derivatives ◽  
Exposure Response ◽  
Oral Doses

ABSTRACT We examined the effects of praziquantel and the artemisinins on adult Echinostoma caproni. In vitro, both praziquantel and the artemisinins exhibited exposure-response relationships. In vivo, worm burden reductions of 100% were achieved with single oral doses of praziquantel, artesunate, and artemether at 50, 700, and 1,100 mg/kg of body weight, respectively.

Sign in / Sign up

Export Citation Format

Share Document