Sickling-preventive effects of rutin is associated with modulation of deoxygenated haemoglobin, 2,3-bisphosphoglycerate mutase, redox status and alteration of functional chemistry in sickle erythrocytes

Sickle cell disease (SCD) is a medical condition caused by mutation in a single nucleotide in the β-globin gene. It is a health problem for people in sub-Saharan Africa, the Middle East and India. Orthodox drugs developed so far for SCD focus largely on symptomatic respite of pain and crisis mitigation. We investigated the antisickling effects of chrysin via modulation of deoxy-haemoglobin, 2,3-bisphosphoglycerate mutase, redox homeostasis and alteration of functional chemistry in human sickle erythrocytes. In silico and in vitro methods were adopted for the studies. Chrysin was docked against deoxy-haemoglobin and 2,3-bisphosphoglycerate mutase, with binding energies (−24.064 and −18.171 kcal/mol) and inhibition constant ( K i) of 0.990 µM and 0.993 µM at their active sites through strong hydrophobic and hydrogen bond interactions. Sickling was induced with 2% metabisulphite at 3 h. Chrysin was able to prevent sickling maximally at 2.5 µg/mL and reversed the same at 12.5 µg/mL, by 66.5% and 69.6%, respectively. Treatment with chrysin significantly ( p < 0.05) re-established the integrity of erythrocytes membrane as evident from the observed percentage of haemolysis relative to induced erythrocytes. Chrysin also significantly ( p < 0.05) prevented and reversed lipid peroxidation. Similarly, glutathione and catalase levels were observed to significantly ( p < 0.05) increase with concomitant significant ( p < 0.05) decrease in superoxide dismutase activity relative to untreated. From Fourier-transform infrared results, treatment with chrysin was able to favourably alter the functional chemistry, judging from the shifts and functional groups observed. Sickling-suppressive effects of chrysin may therefore be associated with sequestration of deoxy-haemoglobin, 2,3-bisphosphoglycerate mutase, alteration of redox homeostasis and functional chemistry of sickle erythrocytes.

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Antisickling Effects of Quercetin may be Associated with Modulation of Deoxyhaemoglobin, 2, 3-bisphosphoglycerate mutase, Redox Homeostasis and Alteration of Functional Chemistry in Human Sickle Erythrocytes.

Annals of Science and Technology ◽

10.2478/ast-2019-0005 ◽

2019 ◽

Vol 4 (1) ◽

pp. 38-47 ◽

Cited By ~ 2

Author(s):

Aliyu Muhammad ◽

Aliyu Dahiru Waziri ◽

Gilead Ebiegberi Forcados ◽

Babangida Sanusi ◽

Hadiza Sani ◽

...

Keyword(s):

Sickle Cell Anaemia ◽

Redox Homeostasis ◽

In Vitro Models ◽

Binding Energies ◽

Hydrogen Bond Interactions ◽

Sickle Erythrocyte ◽

Sickle Erythrocytes ◽

Catalytic Sites ◽

Bisphosphoglycerate Mutase

AbstractIt is now glaring that sickle cell anaemia is still one of the highest leading inbred hemoglobinopathy amongst Africans. This study examined the antisickling effects of quercetin via modulation of deoxy-haemoglobin, redox homeostasis and alteration of functional chemistry in human sickle erythrocyte using in silico and in vitro models while espousing preventive and curative approaches. Quercetin was docked against deoxy-haemoglobin and 2, 3-bisphosphoglycerate mutase, with binding energies (−30.427 and −21.106 kcal/mol) and Ki of 0.988μM and 0.992μM at their catalytic sites via strong hydrophobic and hydrogen bond interactions. Induction of sickling was done using 2% metabisulphite at 3h. Treatment with quercetin prevented sickling outstandingly at 5.0μg/mL and reversed same at 7.5μg/mL, 83.6% and 75.9%, respectively. Quercetin also significantly (P<0.05) maintained the integrity of erythrocyte membrane apparently from the observed % haemolysis relative to untreated. Quercetin significantly (P<0.05) prevented and counteracted lipid peroxidation while stimulating GSH and CAT levels which were detected to considerably (P<0.05) increase with simultaneous significant (P<0.05) reduction in SOD level based on curative approach. Umpiring from our FTIR results, a favorable alteration in the part of functional chemistry in terms of shifts (bend and stretches) and functional groups were observed relative to the induced erythrocyte/untreated. Thus, antisickling effects of quercetin may be associated with modulation of deoxy-haemoglobin, redox homeostasis and alteration of functional chemistry in human sickle erythrocytes.

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Decision letter for "Old age‐associated enrichment of peripheral T regulatory cells and altered redox status in pulmonary tuberculosis patients"

10.1002/eji.201948261/v1/decision1 ◽

2019 ◽

Keyword(s):

Pulmonary Tuberculosis ◽

Old Age ◽

T Regulatory Cells ◽

Redox Status ◽

Regulatory Cells ◽

Tuberculosis Patients

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Intestinal digestibility of selected minerals, growth performance and meat quality in turkeys fed diets supplemented with different sources and levels of zinc

Annals of Animal Science ◽

10.2478/aoas-2020-0093 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Kamil Otowski ◽

Aleksandra Drażbo ◽

Katarzyna Ognik ◽

Krzysztof Kozłowski

Keyword(s):

Growth Performance ◽

Meat Quality ◽

Redox Status ◽

Bursa Of Fabricius ◽

Breast Meat ◽

Zn Addition ◽

Inclusion Level ◽

Dietary Treatments ◽

Different Sources ◽

Intestinal Digestibility

AbstractThe aim of this study was to determine whether dietary supplementation with zinc oxide nanoparticales (NP-ZnO) as a substitute for the conventional ZnO affects the intestinal digestibility of selected minerals, growth performance and meat quality in turkeys. The replacement of ZnO with NP-ZnO had no effect on the intestinal digestibility of Zn, Cu, Fe and Ca, whereas the lowest dose of supplemental Zn reduced Zn digestibility. The applied inclusion levels and sources of Zn had no effect on the growth performance (except the feed intake) of turkeys, including liveability. No differences in the relative weights of the heart, spleen and bursa of Fabricius (except the liver), or the weights of the femur and tibia were found between the dietary treatments. Neither the dose nor the source of supplemental Zn influenced carcass dressing percentage or the share of breast, thigh and drumstick muscles in the carcass. In comparison with the highest and moderate doses of Zn, the lowest inclusion level of Zn contributed to increased yellowness of breast meat (P=0.005). The analyzed doses and sources of supplemental Zn exerted varied effects on the redox status of fresh and frozen breast meat. In conclusion, the growth performance of turkeys, carcass yield and composition as well as the redox status of fresh and frozen breast meat were generally similar, regardless of the dietary source and level of Zn. The beneficial effect of Zn addition at 100 mg/kg was improved Zn and Ca digestibility, and increased redness of breast meat.

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Effect of carvedilol on the redox-status of plasma low-molecular-weight aminothyols in rats with acute cerebral ischemia

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2018.03.12-18 ◽

2018 ◽

pp. 12-18

Author(s):

К.А. Никифорова ◽

В.В. Александрин ◽

П.О. Булгакова ◽

А.В. Иванов ◽

Э.Д. Вирюс ◽

...

Keyword(s):

Molecular Weight ◽

Cerebral Ischemia ◽

Carotid Arteries ◽

Redox Status ◽

Global Cerebral Ischemia ◽

Low Molecular Weight ◽

Adrenergic Antagonist ◽

Acute Cerebral Ischemia ◽

Common Carotid Arteries ◽

Reduced Forms

Цель. Установить влияние неспецифического адреноблокатора карведилола на редокс-статус низкомолекулярных аминотиолов (цистеин, гомоцистеин, глутатион) в плазме крови при моделировании глобальной ишемии головного мозга у крыс. Методика. Нами была использована модель глобальной ишемии (пережатие общих сонных артерий с геморрагией длительностью 15 мин). Препарат вводили за 1 ч до операции. Уровни аминотиолов измеряли через 40 мин после начала реперфузии. Анализ уровня аминотиолов проводили методом жидкостной хроматографии. Результаты. Установлено, что у крыс, не подвергавшихся ишемии, карведилол в дозе 10 мг/кг вызывает рост редокс-статуса цистеина и глутатиона (в 3 и 3,5 раза соответственно по сравнению с контролем, p = 0,04 и p = 0,008) за счет увеличения их восстановленных форм. При ишемии данного эффекта не наблюдалось. Редокс-статус у крыс с ишемией на фоне карведилола (Цис = 0,85 ± 0,14%, Глн = 1,8 ± 0,7%, Гцис = 1,1 ± 0,8%) оставался таким же низким, как и у крыс с ишемией без введения карведилола (р > 0,8). Заключение. Полученный результат демонстрирует, что в условиях ишемии головного мозга карведилол не оказывает эффекта на гомеостаз аминотиолов плазмы крови, несмотря на выраженный антиоксидантный эффект в нормальных условиях. Aim. Effect of a nonspecific adrenergic antagonist carvedilol on the redox status of plasma low-molecular-weight aminothiols (cysteine, homocysteine, glutathione) was studied in rats with global cerebral ischemia (occlusion of common carotid arteries with hemorrhage). Methods. A model of global ischemia (occlusion of common carotid arteries with 15-min hemorrhage) was used. The drugs were administered one hour before the operation. Aminothiol levels were measured by HPLC with UV detection at 40 minutes after the onset of reperfusion. Results. Carvedilol 10 mg/kg increased the redox status of cysteine and glutathione in rats not exposed to ischemia (3 and 3.5 times, respectively, compared with the control, p = 0.04 and p = 0.008, respectively) but not of homocysteine, by increasing their reduced forms. However, this effect was not observed in ischemia. In rats with ischemia treated with carvedilol, the redox status (Cys = 0.85 ± 0.14%, GSH = 1.8 ± 0.7%, Hcys = 1.1 ± 0.8%) remained low similar to that in rats with ischemia not treated with carvedilol (p >0.8, 0.8, and 0.9, respectively). Conclusion. Carvedilol did not affect the homeostasis of blood plasma thiols in cerebral ischemia despite the pronounced antioxidant effect under the normal conditions.

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Combining dietary scGOS:lcFOS and n-3 PUFA did not lead to additional preventive effects in cow’s milk allergy in female mice

10.26226/morressier.5acdc65fd462b8029238df32 ◽

2018 ◽

Author(s):

Kirsten Szklany

Keyword(s):

Cow’S Milk Allergy ◽

Cow’S Milk ◽

Milk Allergy ◽

Cow's Milk ◽

Female Mice ◽

Cow's Milk Allergy ◽

Preventive Effects

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Type 2 diabetes mellitus in patients with acute ischemiс stroke is associated with a decrease in plasma glutathione levels

Russian neurological Journal ◽

10.30629/2658-7947-2020-25-5-29-35 ◽

2020 ◽

Vol 25 (5) ◽

pp. 29-35

Author(s):

M. Yu. Maksimova ◽

A. V. Ivanov ◽

K. A. Nikiforova ◽

F. R. Ochtova ◽

E. T. Suanova ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Redox Status ◽

Reduced Form ◽

Glutathione Level ◽

Total Glutathione ◽

Diabetes Mellitus Group ◽

Reduced Forms

Ischemic stroke (IS) and type 2 diabetes mellitus are factors that aﬀect the homeostasis of low-molecularweight aminothiols (cysteine, homocysteine, glutathione etc.). It has already been shown that IS in the acute period led to a decrease a level of reduced forms of aminothiols, but it is not clear whether type 2 diabetes mellitus has a noticeable eﬀect there. Objective: to reveal the features of homeostasis of aminothiols in patients with type 2 diabetes mellitus in acute IS. Material and methods. The study involved 76 patients with primary middle cerebral artery IS in the first 10–24 hours after development of neurological symptoms. Group 1 included 15 patients with IS and type 2 diabetes mellitus, group 2 — 61 patients with IS and stress hyperglycemia. Their total plasma levels of cysteine, homocysteine, and glutathione, their reduced forms, and redox status were determined at admission (in the first 24 hours after IS). Results. There was a decrease in the level of total glutathione level (1.27 vs. 1.65 μM, p = 0.021), as well as its reduced form (0.03 vs. 0.04 μM, p = 0.007) in patients with IS and type 2 diabetes mellitus. Patients with type 2 diabetes mellitus who had a low redox status of homocysteine (0.65–1.2%) and glutathione (0.7–2.0%) were also characterized by a decrease in total glutathione level (p = 0.02; p = 0.03). Conclusion. Thus, type 2 diabetes mellitus is associated with a decrease in the level of total glutathione in acute IS. Probably, type 2 diabetes mellitus is characterized by a particular relationship between the metabolism of homocysteine, glutathione and glucose. Therefore, the search for homocysteine-dependent approaches to correct glutathione metabolism in type 2 diabetes mellitus may be of interest as an adjuvant therapy for IS.

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