scholarly journals Investigation of Andrographolide Effect on Non-Infected Red Blood Cells Using the 1H-NMR-Based Metabolomics Approach

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 486
Author(s):  
Ashraf Ahmad Issa Alapid ◽  
Roslaini Abd. Majid ◽  
Zaid O. Ibraheem ◽  
Ahmed Mediani ◽  
Intan Safinar Ismail ◽  
...  
Keyword(s):  
Data Analysis ◽  
Red Blood Cells ◽  
1H Nmr ◽  
Blood Cells ◽  
Metabolic Pathways ◽  
Metabolic Changes ◽  
Glutamine Metabolism ◽  
Proton Nuclear Magnetic Resonance ◽  
Glutathione Metabolism ◽  
Pharmacological Effects

Andrographolide (AG) has been shown to have several medicinal and pharmaceutical effects, such as antimicrobial, anti-inflammatory, antioxidant, anti-diabetic, and anti-malarial activities. Moreover, studies to assess the pharmacological effect of AG on the metabolic changes of uninfected red blood cells (uRBCs) have not yet been investigated. This study aims to evaluate the pharmacological effects of AG compared to chloroquine (CQ) on the metabolic variations of uRBCs in vitro using a proton nuclear magnetic resonance (1H-NMR)-based metabolomics approach coupled with multivariate data analysis (MVDA). Forty-one metabolites were successfully identified by 1H-NMR. The results of the unsupervised data analysis principal component analysis (PCA) showed ideal differentiation between AG and CQ. PC1 and PC2 accounted for 71.4% and 17.7% of the explained variation, respectively, with a total variance of 89.10%. Based on S-plot and VIP values, a total of 28 and 32 metabolites were identified as biomarkers in uRBCs-AG and uRBCs-CQ, respectively. In uRBCs treated with AG, ten metabolic pathways were determined to be disturbed, including riboflavin metabolism, d-glutamate and d-glutamine metabolism, phenylalanine metabolism, glutathione metabolism, proline and arginine metabolism, arginine biosynthesis, citrate cycle, glycolysis/gluconeogenesis, and pyruvate metabolism as well as alanine, aspartate, and glutamate metabolism. In contrast, in CQ-treated uRBCs, nine affected metabolic pathways were determined, which involved the same metabolic pathways for uRBCs-AG, except for glutathione metabolism. These findings suggest an evident relationship between AG and CQ associated with metabolic changes in intact RBCs after being exposed to the treatment. The metabolomics results could allow useful comprehensive insights into the underlying mechanism of the action of AG and CQ on red blood cells. Consequently, the 1H-NMR-based metabolomics approach was successfully utilized to identify the pharmacological effects of AG and CQ on the metabolic variations of uRBCs.

scholarly journals Regulation of intracellular glutathione levels in erythrocytes infected with chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum

2002 ◽  
Vol 368 (3) ◽  
pp. 761-768 ◽  
Author(s):  
Svenja MEIERJOHANN ◽  
Rolf D. WALTER ◽  
Sylke MÜLLER
Keyword(s):  
Oxidative Stress ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Differential Susceptibility ◽  
Protozoan Parasite ◽  
Chloroquine Resistance ◽  
Glutathione Metabolism ◽  
Glutathione Synthesis ◽  
Intracellular Glutathione ◽  
Glutamylcysteine Synthetase

Malaria is one of the most devastating tropical diseases despite the availability of numerous drugs acting against the protozoan parasite Plasmodium in its human host. However, the development of drug resistance renders most of the existing drugs useless. In the malaria parasite the tripeptide glutathione is not only involved in maintaining an adequate intracellular redox environment and protecting the cell against oxidative stress, but it has also been shown that it degrades non-polymerized ferriprotoporphyrin IX (FP IX) and is thus implicated in the development of chloroquine resistance. Glutathione levels in Plasmodium-infected red blood cells are regulated by glutathione synthesis, glutathione reduction and glutathione efflux. Therefore the effects of drugs that interfere with these metabolic processes were studied to establish possible differences in the regulation of the glutathione metabolism of a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodiumfalciparum. Growth inhibition of P. falciparum 3D7 by d,l-buthionine-(S,R)sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase (γ-GCS), and by Methylene Blue (MB), an inhibitor of gluta thione reductase (GR), was significantly more pronounced than inhibition of P.falciparum Dd2 growth by these drugs. These results correlate with the higher levels of total glutathione in P. falciparum Dd2. Short-term incubations of Percoll-enriched trophozoite-infected red blood cells in the presence of BSO, MB and N,N1-bis(2-chloroethyl)-N-nitrosourea and subsequent determinations of γ-GCS activities, GR activities and glutathione disulphide efflux revealed that maintenance of intracellular glutathione in P. falciparum Dd2 is mainly dependent on glutathione synthesis whereas in P. falciparum 3D7 it is regulated via GR. Generally, P. falciparum Dd2 appears to be able to sustain its intracellular glutathione more efficiently than P. falciparum 3D7. In agreement with these findings is the differential susceptibility to oxidative stress of both parasite strains elicited by the glucose/glucose oxidase system.

scholarly journals Changes in hepatic metabolic profile during the evolution of STZ-induced diabetic rats via an 1H NMR-based metabonomic investigation

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Minjiang Chen ◽  
Hong Zheng ◽  
Min Xu ◽  
Liangcai Zhao ◽  
Qianqian Zhang ◽  
...  
Keyword(s):  
Amino Acids ◽  
1H Nmr ◽  
Metabolic Pathways ◽  
Metabolic Profile ◽  
Diabetic Rats ◽  
Proton Nuclear Magnetic Resonance ◽  
Control Group ◽  
Resonance Spectroscopy ◽  
Discriminate Analysis ◽  
Protective Function

Abstract Background: The present study aimed to explore the changes in the hepatic metabolic profile during the evolution of diabetes mellitus (DM) and verify the key metabolic pathways. Methods: Liver samples were collected from diabetic rats induced by streptozotocin (STZ) and rats in the control group at 1, 5, and 9 weeks after STZ administration. Proton nuclear magnetic resonance spectroscopy (1H NMR)-based metabolomics was used to examine the metabolic changes during the evolution of DM, and partial least squares-discriminate analysis (PLS-DA) was performed to identify the key metabolites. Results: We identified 40 metabolites in the 1H NMR spectra, and 11 metabolites were further selected by PLS-DA model. The levels of α-glucose and β-glucose, which are two energy-related metabolites, gradually increased over time in the DM rats, and were significantly greater than those of the control rats at the three-time points. The levels of choline, betaine, and methionine decreased in the DM livers, indicating that the protective function in response to liver injury may be undermined by hyperglycemia. The levels of the other amino acids (leucine, alanine, glycine, tyrosine, and phenylalanine) were significantly less than those of the control group during DM development. Conclusions: Our results suggested that the hepatic metabolic pathways of glucose, choline-betaine-methionine, and amino acids were disturbed during the evolution of diabetes, and that choline-betaine-methionine metabolism may play a key role.

scholarly journals Effects of aged stored autologous red blood cells on human plasma metabolome

2019 ◽  
Vol 3 (6) ◽  
pp. 884-896 ◽  
Author(s):  
Angelo D’Alessandro ◽  
Julie A. Reisz ◽  
Yingze Zhang ◽  
Sarah Gehrke ◽  
Keisha Alexander ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Metabolic Changes ◽  
Complete Analysis ◽  
Diethylhexyl Phthalate ◽  
Plasma Hemoglobin ◽  
Plasma Metabolome ◽  
Forearm Circulation ◽  
Circulating Levels ◽  
Free Plasma

Abstract Cold storage of blood for 5 to 6 weeks has been shown to impair endothelial function after transfusion and has been associated with measures of end-organ dysfunction. Although the products of hemolysis, such as cell-free plasma hemoglobin, arginase, heme, and iron, in part mediate these effects, a complete analysis of transfused metabolites that may affect organ function has not been evaluated to date. Blood stored for either 5 or 42 days was collected from 18 healthy autologous volunteers, prior to and after autologous transfusion into the forearm circulation, followed by metabolomics analyses. Significant metabolic changes were observed in the plasma levels of hemolytic markers, oxidized purines, plasticizers, and oxidized lipids in recipients of blood stored for 42 days, compared with 5 days. Notably, transfusion of day 42 red blood cells (RBCs) increased circulating levels of plasticizers (diethylhexyl phthalate and derivatives) by up to 18-fold. Similarly, transfusion of day 42 blood significantly increased circulating levels of proinflammatory oxylipins, including prostaglandins, hydroxyeicosatrienoic acids (HETEs), and dihydroxyoctadecenoic acids. Oxylipins were the most significantly increasing metabolites (for 9-HETE: up to ∼41-fold, P = 3.7e-06) in day 42 supernatants. Measurements of arginine metabolism confirmed an increase in arginase activity at the expense of nitric oxide synthesis capacity in the bloodstream of recipients of day 42 blood, which correlated with measurements of hemodynamics. Metabolic changes in stored RBC supernatants impact the plasma metabolome of healthy transfusion recipients, with observed increases in plasticizers, as well as vasoactive, pro-oxidative, proinflammatory, and immunomodulatory metabolites after 42 days of storage.

scholarly journals Transfusion of packed red blood cells at the end of shelf life is associated with increased risk of mortality – a pooled patient data analysis of 16 observational trials

Haematologica ◽  
2018 ◽  
Vol 103 (9) ◽  
pp. 1542-1548 ◽  
Author(s):  
Monica S.Y. Ng ◽  
Michael David ◽  
Rutger A. Middelburg ◽  
Angela S.Y. Ng ◽  
Jacky Y. Suen ◽  
...  
Keyword(s):  
Data Analysis ◽  
Red Blood Cells ◽  
Shelf Life ◽  
Blood Cells ◽  
Patient Data ◽  
Packed Red Blood Cells ◽  
Risk Of Mortality ◽  
Increased Risk

scholarly journals The Antifungal Potential of Sarvacrol against Penicillium digitatum through 1H-NMR Based Metabolomics Approach

2019 ◽  
Author(s):  
Chunpeng Wan ◽  
Yuting Shen ◽  
Muhammad Farrukh Nisar ◽  
Wenwen Qi ◽  
Chuying Chen ◽  
...  
Keyword(s):  
1H Nmr ◽  
Citrus Fruit ◽  
Metabolic Changes ◽  
Penicillium Digitatum ◽  
Glutathione Metabolism ◽  
Strong Positive Correlation ◽  
Food Preservative ◽  
Metabolomic Profiling ◽  
Green Mold ◽  
Antifungal Potential

Carvacrol has long been studied for its natural antifungal potential and food preservative. But the exact mode of its action remained highly complex as a general, but especially for Penicillium digitatum (P. digitatum) largely remained unexplored. Herein, a 1H-NMR-based metabolomic technique was used to investigate the antifungal mechanism of carvacrol. The metabolomic profiling data showed that alanine, aspartate, glutamate and glutathione metabolism were imbalanced in the fungal hyphae. A strong positive correlation was seen between aspartate, glutamate, alanine and glutamine, while negative correlation among glutathione and lactate. These metabolic changes revealed that carvacrol-induced oxidative stress had disturbed the energy production and amino acid metabolism of P. digitatum. Current study will improve the understanding of the metabolic changes posed by plant-based fungicides in order to control citrus fruit green mold caused by P. digitatum. Moreover, the study will provided certain experimental and theoretical basis for the development of novel citrus fruit preservatives.

Circulation of Red Blood Cells Having High Levels of 2,3-Bisphosphoglycerate Protects Rat Brain From Ischemic Metabolic Changes During Hemodilution

Stroke ◽  
1995 ◽  
Vol 26 (8) ◽  
pp. 1431-1437 ◽  
Author(s):  
Hideo Kimura ◽  
Naotaka Hamasaki ◽  
Masaaki Yamamoto ◽  
Masamichi Tomonaga
Keyword(s):  
Red Blood Cells ◽  
Rat Brain ◽  
Blood Cells ◽  
Metabolic Changes
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